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1
Holan, Vladimir, Katerina Palacka, and Barbora Hermankova. "Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials." Cells 10, no. 3 (March 7, 2021): 588. http://dx.doi.org/10.3390/cells10030588.
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Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.
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Balicka, A., M. Lapsanska, and A. Trbolova. "Retinal Diseases of Senior Dogs." Folia Veterinaria 64, no. 4 (December 1, 2020): 71–77. http://dx.doi.org/10.2478/fv-2020-0040.
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AbstractAging consists of a physiological decline of an organism’s functional activity. During the aging process, the structural and functional changes of the retina can be observed. In most cases, progressive vision loss occurs due to the age related changes of the anterior segment. Retinal diseases, characteristic for senior dogs are: retinal detachment, hypertensive chorioretinopathy, sudden acquired retinal degeneration syndrome (SARDS), progressive retinal atrophy (PRA), glaucoma, retinopathy, cystoid degeneration and neoplasms. The examination of the retina in senior dogs is based on: ophthalmoscopic examination, electroretinography, spectral-domain optical coherence tomography (AD-OCT) and if necessary, histopathological examinations. Comprehensive knowledge regarding the senior dog’s health, significantly increases their quality of life.
3
Nagamani, Gilakara Muni, and Theertagiri Sudhakar. "An improved dynamic-layered classification of retinal diseases." IAES International Journal of Artificial Intelligence (IJ-AI) 13, no. 1 (March 1, 2024): 417. http://dx.doi.org/10.11591/ijai.v13.i1.pp417-429.
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<span>Retina is main part of the human eye and every disease shows the effect on retina. Eye diseases such as choroidal neovascularization (CNV), DRUSEN, diabetic macular edema (DME) are the main retinal diseases that damage the retina and if these damages are identified in the later stages, it is very difficult to reverse the vision for these retinal diseases. Optical coherence tomography (OCT) is a non-nosy image testing for finding the retinal diseases. OCT mainly collects the cross-section images of retina. Deep learning (DL) is used to analyze the patterns in several complex research applications especially in the disease prediction. In DL, multiple layers give the accurate detection of abnormalities in the retinal images. In this paper, an improved dynamic-layered classification (IDLC) is introduced to classify retinal diseases based on their abnormality. Image filters are used to filter the noise present in the input images. ResNet is the pre-trained model which is used to train the features of retinal diseases. Convolutional neural networks (CNN) are the DL model used to analyze the OCT image. The dataset consists of three types of OCT disease datasets from Kaggle. Evaluation results show the performance of IDLC compared with state-of-art algorithms. A better performance is obtained by using the IDLC and achieved the better accuracy. </span>
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Greco, Jordan A., Nicole L. Wagner, Ralph J. Jensen, Daniel B. Lawrence, Matthew J. Ranaghan, Megan N. Sandberg, Daniel J. Sandberg, and Robert R. Birge. "Activation of retinal ganglion cells using a biomimetic artificial retina." Journal of Neural Engineering 18, no. 6 (December 1, 2021): 066027. http://dx.doi.org/10.1088/1741-2552/ac395c.
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Abstract Objective. Biomimetic protein-based artificial retinas offer a new paradigm for restoring vision for patients blinded by retinal degeneration. Artificial retinas, comprised of an ion-permeable membrane and alternating layers of bacteriorhodopsin (BR) and a polycation binder, are assembled using layer-by-layer electrostatic adsorption. Upon light absorption, the oriented BR layers generate a unidirectional proton gradient. The main objective of this investigation is to demonstrate the ability of the ion-mediated subretinal artificial retina to activate retinal ganglion cells (RGCs) of degenerated retinal tissue. Approach. Ex vivo extracellular recording experiments with P23H line 1 rats are used to measure the response of RGCs following selective stimulation of our artificial retina using a pulsed light source. Single-unit recording is used to evaluate the efficiency and latency of activation, while a multielectrode array (MEA) is used to assess the spatial sensitivity of the artificial retina films. Main results. The activation efficiency of the artificial retina increases with increased incident light intensity and demonstrates an activation latency of ∼150 ms. The results suggest that the implant is most efficient with 200 BR layers and can stimulate the retina using light intensities comparable to indoor ambient light. Results from using an MEA show that activation is limited to the targeted receptive field. Significance. The results of this study establish potential effectiveness of using an ion-mediated artificial retina to restore vision for those with degenerative retinal diseases, including retinitis pigmentosa.
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Shelke, D. A., and S. Shirolkar. "DRUG DELIVERY TO RETINA: A REVIEW." INDIAN DRUGS 56, no. 09 (September 28, 2019): 7–21. http://dx.doi.org/10.53879/id.56.09.11991.
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The drug delivery to posterior segment especially to retina of eye is difficult due to various barriers. The diseases affecting the retina of eye are increasing and hence there is need to develop approaches for drug delivery to retina. This review describes the anatomy of retina, barriers associated with it, and diseases of retina. The drug delivery to retina by systemic, topical, intravitreal injection, intravitreal implant along with advance nanotechnology based and transporter mediated drug delivery is discussed here. The recent technologies in retinal drug delivery are also discussed to give comprehensive recent information about retinal drug delivery
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Makabe, Kenichi, Sunao Sugita, Yoko Futatsugi, and Masayo Takahashi. "Dynamics of Cyclooxygenase-1 Positive Microglia/Macrophage in the Retina of Pathological Model Mice as a Biomarker of the Retinal Inflammatory Diseases." International Journal of Molecular Sciences 22, no. 7 (March 25, 2021): 3396. http://dx.doi.org/10.3390/ijms22073396.
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In an intraocular inflammatory state, microglia residing in the retina become active and migrate inside the retina. In this study, we investigated whether cyclooxygenase-1 (COX-1) expressed by retinal microglia/macrophage can be a biomarker for the diagnosis of retinal diseases. COX-1 was immunopositive in microglia/macrophage and neutrophils, while COX-2 was immunopositive in astrocytes and neurons in the inner layer of normal retina. The number of COX-1 positive cells per section of the retinal tissue was 14 ± 2.8 (mean ± standard deviation) in normal mice, which showed significant increase in the lipopolysaccharide (LPS)-administrated model (62 ± 5.0, p = 8.7 × 10−9). In addition to microglia, we found neutrophils that were positive for COX-1. In the early stage of inflammation in the experimental autoimmune uveoretinitis (EAU), COX-1 positive cells, infiltrating from the ciliary body into the retinal outer nuclear layer, were observed. The number of infiltrating COX-1 positive cells correlated with the severity of EAU. Taken together, the increased number of COX-1 positive microglia/macrophage with morphological changes were observed in the retinas of retinal inflammatory disease models. This suggests that COX-1 can be a marker of disease-related activities of microglia/macrophage, which should be useful for the diagnosis of retinal diseases.
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Sun, Ye, and Lois E. H. Smith. "Retinal Vasculature in Development and Diseases." Annual Review of Vision Science 4, no. 1 (September 15, 2018): 101–22. http://dx.doi.org/10.1146/annurev-vision-091517-034018.
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The retina is one of the most metabolically active tissues in the body, consuming high levels of oxygen and nutrients. A well-organized ocular vascular system adapts to meet the metabolic requirements of the retina to ensure visual function. Pathological conditions affect growth of the blood vessels in the eye. Understanding the neuronal biological processes that govern retinal vascular development is of interest for translational researchers and clinicians to develop preventive and interventional therapeutics for vascular eye diseases that address early drivers of abnormal vascular growth. This review summarizes the current knowledge of the cellular and molecular processes governing both physiological and pathological retinal vascular development, which is dependent on the interaction among retinal cell populations, including neurons, glia, immune cells, and vascular endothelial cells. We also review animal models currently used for studying retinal vascular development.
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Li, Yan, Ting Luo, and Hong-Bin Lyu. "Therapeutic potential of iron chelators in retinal vascular diseases." International Journal of Ophthalmology 16, no. 11 (November 18, 2023): 1899–910. http://dx.doi.org/10.18240/ijo.2023.11.24.
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Iron is one of the necessary metal elements in the human body. There are numerous factors that control the balance of iron metabolism, and its storage and transportation mechanisms are intricate. As one of the most energy-intensive tissues in the body, the retina is susceptible to iron imbalance. The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species. This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis, eventually resulting in retinal dysfunction. The blood-retina-retinal barrier is eventually harmed by oxidative stress and elevated inflammation, which are characteristics of retinal vascular disorders. The pathophysiology of retinal vascular disorders may be significantly influenced by iron. Recently, iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating. Therefore, iron neutralization is considered to be a new and potentially useful therapeutic strategy. This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.
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Schilardi, Giulia, Jakub Kralik, and Sonja Kleinlogel. "Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling." International Journal of Molecular Sciences 24, no. 18 (September 18, 2023): 14207. http://dx.doi.org/10.3390/ijms241814207.
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Loss of photoreceptors in retinal degenerative diseases also impacts the inner retina: bipolar cell dendrites retract, neurons rewire, and protein expression changes. ON-bipolar cells (OBCs) represent an attractive target for optogenetic vision restoration. However, the above-described maladaptations may negatively impact the quality of restored vision. To investigate this question, we employed human post-mortem retinas and transgenic rd1_Opto-mGluR6 mice expressing the optogenetic construct Opto-mGluR6 in OBCs and carrying the retinal degeneration rd1 mutation. We found significant changes in delayed rectifier potassium channel expression in OBCs of degenerative retinas. In particular, we found an increase in Kv1.3 expression already in early stages of degeneration. Immunohistochemistry localized Kv1.3 channels specifically to OBC axons. In whole-cell patch-clamp experiments, OBCs in the degenerated murine retina were less responsive, which could be reversed by application of the specific Kv1.3 antagonist Psora-4. Notably, Kv1.3 block significantly increased the amplitude and kinetics of Opto-mGluR6-mediated light responses in OBCs of the blind retina and increased the signal-to-noise ratio of light-triggered responses in retinal ganglion cells. We propose that reduction in Kv1.3 activity in the degenerated retina, either by pharmacological block or by KCNA3 gene silencing, could improve the quality of restored vision.
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Dolar-Szczasny, Joanna, Anna Święch-Zubilewicz, and Jerzy Mackiewicz. "Innovation in retinal diseases – ultra-widefield imaging." Polish Journal of Public Health 125, no. 1 (March 1, 2015): 14–16. http://dx.doi.org/10.1515/pjph-2015-0014.
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Abstract The understanding of retinal disease has evolved rapidly with a growing number of clinical evidence supplied by ultrawidefield retinal imaging. Optos 200Tx ultra-widefield retinal imaging system uses a scanning laser ophthalmoscope, as well as an ellipsoid mirror. This creates a possibility of making a virtual focal point inside the eye and, in turn, enables the system to simultaneously make a single capture of the central retina and periphery. This system offers multimodal ultra-widefield imaging, including color photographs, fundus autofluorescence images, red-free images and fluorescein angiography (FA), allowing visualization of the retinal circulation. For color photographs, green and red lasers are used simultaneously to allow visualization of retinal substructures from the sensory retina and retinal pigment epithelium to the choroid. In our clinic ultra-widefield fluorescein angiography has became an elegant diagnostic imaging modality that has improved our ability to diagnose and plan treatment strategies. In the future widefield imaging will probably be coupled with OCT (optical coherence tomography) option to better evaluate retinal pathologies in the periphery.
11
TUNCER, Samuray, and Ecem ÜSTÜNDAŞ UZUN. "Tumors of the Retina, Optic Disc and Retinal Pigment Epithelium." Güncel Retina Dergisi (Current Retina Journal) 8, no. 1 (October 22, 2023): 27–31. http://dx.doi.org/10.37783/crj-0383.
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Vascular tumors of the retina include retinal capillary hemangioma (retinal hemangioblastoma), retinal cavernous hemangioma, retinal racemose hemangioma, and vasoproliferative tumor of the retina. Although they are benign and rare tumors, vascular tumors of the retina are important due to the potential for vision loss through ocular complications, as well as the possibility of morbidity and mortality from accompanying systemic diseases. Ophthalmologists have an important role in diagnosing and implementing necessary screening and treatments. This article will describe the vascular tumors of the retina and optic nerve head.
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Alicia Pricelda. "Tren Terapi Age-Related Macular Degeneration." Cermin Dunia Kedokteran 48, no. 12 (December 1, 2021): 745–47. http://dx.doi.org/10.55175/cdk.v48i12.176.
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Dahulu penyakit retina memiliki prioritas rendah dalam strategi pencegahan kebutaan di negara berkembang karena masih jarang dikenal sebagai penyebab kebutaan, peralatan belum cukup canggih, dan kurangnya tenaga medis sub-spesialistik penyakit retina. Seiring kemajuan ilmu pengetahuan dan teknologi, penyakit retina saat ini diketahui merupakan salah satu penyebab kebutaan utama terutama pada anak. Masih belum banyak pilihan terapi penyakit retina, tetapi pasien berhak mendapatkan diagnosis yang akurat, penjelasan yang baik, dan prognosis yang jelas. Artikel ini membahas salah satu penyakit retina, yaitu age-related macular degeneration (AMD), pengobatan yang tersedia dan yang sedang dikembangkan.
Previously, retinal diseases had low priority in preventing blindness strategies in developing countries because they are rarely known as the cause of blindness, no available sophisticated diagnostic equipment, and also lack of medical personnel with sub-specialties in retinal diseases. With the advancement of science and technology, retinal disease is now currently known as one of the main causes of blindness, especially in children. Limited therapies are currently available, but patients still deserve an accurate diagnosis, good explanation, and a clear prognosis. This article discusses one of the retinal diseases : age-related macular degeneration (AMD), its existing and emerging treatments.
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Martínez-Solís, Isabel, Nuria Acero, Francisco Bosch-Morell, Encarna Castillo, María Eugenia González-Rosende, Dolores Muñoz-Mingarro, Teresa Ortega, María Amparo Sanahuja, and Victoria Villagrasa. "Neuroprotective Potential of Ginkgo biloba in Retinal Diseases." Planta Medica 85, no. 17 (July 2, 2019): 1292–303. http://dx.doi.org/10.1055/a-0947-5712.
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AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.
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Mueller-Buehl, Ana M., Torsten Buehner, Christiane Pfarrer, Leonie Deppe, Laura Peters, Burkhard H. Dick, and Stephanie C. Joachim. "Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas." Cells 10, no. 12 (December 18, 2021): 3575. http://dx.doi.org/10.3390/cells10123575.
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Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular degeneration, or diabetic retinopathy. In consideration of these diseases, it is also evidenced that the immune system, including the complement system and its activation, plays an important role. Suitable models to investigate neuroretinal diseases are organ cultures of porcine retina. Based on an established model, the role of the complement system was studied after the induction of oxidative stress or hypoxia. Both stressors led to a loss of retinal ganglion cells (RGCs) accompanied by apoptosis. Hypoxia activated the complement system as noted by higher C3+ and MAC+ cell numbers. In this model, activation of the complement cascade occurred via the classical pathway and the number of C1q+ microglia was increased. In oxidative stressed retinas, the complement system had no consideration, but strong inflammation took place, with elevated TNF, IL6, and IL8 mRNA expression levels. Together, this study shows that hypoxia and oxidative stress induce different mechanisms in the porcine retina inducing either the immune response or an inflammation. Our findings support the thesis that the immune system is involved in the development of retinal diseases. Furthermore, this study is evidence that both approaches seem suitable models to investigate undergoing pathomechanisms of several neuroretinal diseases.
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Charles, Elizabeth, Sunil Joshi, John D. Ash, Barbara A. Fox, A. Darise Farris, David J. Bzik, Mark L. Lang, and Ira J. Blader. "CD4 T-Cell Suppression by Cells from Toxoplasma gondii-Infected Retinas Is Mediated by Surface Protein PD-L1." Infection and Immunity 78, no. 8 (May 24, 2010): 3484–92. http://dx.doi.org/10.1128/iai.00117-10.
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ABSTRACT In the inflamed retina, CD4+ T cells can cause retinal damage when they are not properly regulated. Since tissue expression of major histocompatibility complex (MHC) class II and costimulatory molecules is a key mechanism for regulating effector T cells, we tested the hypothesis that upregulation of these proteins in the retina contributes to the regulation of CD4 T cells. Here we report that in retinas infected with the protozoan parasite Toxoplasma gondii, MHC class II is upregulated on infiltrating leukocytes as well as on resident retinal cells, including photoreceptors. Flow cytometric analysis indicated that B7 costimulatory family members (CD80, CD86, ICOS-L, and programmed death ligand 2 [PD-L2]) were not expressed on class II+ cells. In contrast, PD-L1 (also named B7-H1 or CD274) was expressed on the majority of both hematopoietic and resident retinal MHC class II-expressing cells. Retinal cells from Toxoplasma-infected animals were able to suppress T-cell activation in a PD-L1-dependent manner. Finally, we demonstrate that the expression of MHC class II and PD-L1 was critically dependent on gamma interferon (IFN-γ) expression. These data suggest that retinal MHC class II and PD-L1 expression is a novel mechanism by which the retina protects itself from CD4 T-cell-mediated immune damage in ocular toxoplasmosis and other types of retinal immune responses.
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Szabelska, Paulina, Justyna Mędrzycka, Radosław Różycki, and Joanna Gołębiewska. "MODERN DIAGNOSTIC POSSIBILITIES FOR THE ASSESSMENT OF POSTERIOR EYE DISEASES WITH ULTRA-WIDEFIELD IMAGING." Polish Journal of Aviation Medicine, Bioengineering and Psychology 26, no. 2 (March 30, 2023): 17–24. http://dx.doi.org/10.13174/pjambp.30.03.2023.03.
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Abstract: Ultra-widefield retinal imaging is a modern method of imaging the posterior segment of the eye that enables scanning of the entire far periphery of retina. Our study presents the diagnostic possibilities of this technique using Optos California to illustrate pathology anywhere in the retina and provide clinical data from the retinal surface through the choroid.
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Pricelda, Alicia. "Tren Terapi Age-Related Macular Degeneration." Cermin Dunia Kedokteran 48, no. 12 (December 8, 2021): 745. http://dx.doi.org/10.55175/cdk.v48i12.1584.
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<p>Dahulu penyakit retina memiliki prioritas rendah dalam strategi pencegahan kebutaan di negara berkembang karena masih jarang dikenal sebagai penyebab kebutaan, peralatan belum cukup canggih, dan juga kurangnya tenaga medis sub-spesialistik penyakit retina. Seiring kemajuan ilmu pengetahuan dan teknologi, penyakit retina saat ini diketahui merupakan salah satu penyebab kebutaan utama terutama pada anak. Masih belum banyak pilihan terapi penyakit retina, tetapi pasien berhak mendapatkan diagnosis yang akurat, penjelasan yang baik, dan prognosis yang jelas. Artikel ini membahas salah satu penyakit retina yaitu age-related macular degeneration (AMD), pengobatan yang tersedia dan yang sedang dikembangkan.</p><p>Previously, retinal diseases had low priority in preventing blindness strategies in developing countries because they are rarely known as the cause of blindness, no available sophisticated diagnostic equipment, and also lack of medical personnel with sub-specialties in retinal diseases. With the advancement of science and technology, retinal disease is now currently known as one of the main causes of blindness, especially in children. Limited therapies are currently available, but patients still deserve an accurate diagnosis, good explanation, and a clear prognosis. This article discusses one of the retinal diseases : age-related macular degeneration (AMD), its existing and emerging treatments.</p>
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Grishina, E. E., A. A. Ryabtseva, O. M. Andryuhina, and A. A. Kovrizhkina. "The role of optical coherence tomography in the diagnosis of the leukemic infiltration of the optic nerve and retina." Russian Ophthalmological Journal 14, no. 4 (December 30, 2021): 46–51. http://dx.doi.org/10.21516/2072-0076-2021-14-4-46-51.
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Even though there are multiple diseases of the optic nerve and the retina in patients with hemoblastosis, their ophthalmoscopic picture is similar in many respects. The purpose of this study is to determine the role of optical coherence tomography (OCT) in the differential diagnosis of various manifestations of hemoblastosis in the fundus. Material and methods. From Jan. 2015 to Jan. 2019, 9 patients (5 men and 4 women aged 29 to 72) with hemoblastosis and lesions of the optic nerve and retina were examined. Results. 5 patients were diagnosed with leukemic infiltration of the optic nerve. The remaining 4 patients had, congestive optic discs (1), occlusion of the central retinal vein (1), anterior ischemic optic neuropathy (1), and bilateral occlusion of the central retinal artery with leukemic infiltration of eye membranes (1). The article describes the ophthalmoscopic pictures and OCT data for the specific diseases. Unlike other diseases of the optic nerve and retina, leukemic infiltration is characterized by a pronounced dense edema in the inner layers of the retina with shielding of the underlying outer layers of the retina. Conclusion. OCT is an important additional method for differential diagnosis of leukemic infiltration and other diseases of the optic nerve and retina in patients with hemoblastosis.
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Querques, Giuseppe, Raimondo Forte, and Eric H. Souied. "Retina and Omega-3." Journal of Nutrition and Metabolism 2011 (2011): 1–12. http://dx.doi.org/10.1155/2011/748361.
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Over the last decade, several epidemiological studies based on food frequency questionnaires suggest that omega-3 polyunsaturated fatty acids could have a protective role in reducing the onset and progression of retinal diseases. The retina has a high concentration of omega-3, particularly DHA, which optimizes fluidity of photoreceptor membranes, retinal integrity, and visual function. Furthermore, many studies demonstrated that DHA has a protective, for example antiapoptotic, role in the retina. From a nutritional point of view, it is known that western populations, particularly aged individuals, have a higher than optimal omega-6/omega-3 ratio and should enrich their diet with more fish consumption or have DHA supplementation. This paper underscores the potential beneficial effect of omega-3 fatty acids on retinal diseases.
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Mat Nor, Mohd N., Ilva D. Rupenthal, Colin R. Green, and Monica L. Acosta. "Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases." International Journal of Molecular Sciences 22, no. 4 (February 10, 2021): 1755. http://dx.doi.org/10.3390/ijms22041755.
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Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.
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Noah Akande, Oluwatobi, Oluwakemi Christiana Abikoye, Aderonke Anthonia Kayode, and Yema Lamari. "Implementation of a Framework for Healthy and Diabetic Retinopathy Retinal Image Recognition." Scientifica 2020 (May 19, 2020): 1–14. http://dx.doi.org/10.1155/2020/4972527.
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The feature extraction stage remains a major component of every biometric recognition system. In most instances, the eventual accuracy of a recognition system is dependent on the features extracted from the biometric trait and the feature extraction technique adopted. The widely adopted technique employs features extracted from healthy retinal images in training retina recognition system. However, literature has shown that certain eye diseases such as diabetic retinopathy (DR), hypertensive retinopathy, glaucoma, and cataract could alter the recognition accuracy of the retina recognition system. This connotes that a robust retina recognition system should be designed to accommodate healthy and diseased retinal images. A framework with two different approaches for retina image recognition is presented in this study. The first approach employed structural features for healthy retinal image recognition while the second employed vascular and lesion-based features for DR retinal image recognition. Any input retinal image was first examined for the presence of DR symptoms before the appropriate feature extraction technique was adopted. Recognition rates of 100% and 97.23% were achieved for the healthy and DR retinal images, respectively, and a false acceptance rate of 0.0444 and a false rejection rate of 0.0133 were also achieved.
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Puddu, Alessandra, and Davide Maggi. "Anti-Inflammatory Effects of GLP-1R Activation in the Retina." International Journal of Molecular Sciences 23, no. 20 (October 17, 2022): 12428. http://dx.doi.org/10.3390/ijms232012428.
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Glucagon-like peptide-1 (GLP-1) is an incretin hormone, mainly produced by enteroendocrine L cells, which participates in the regulation of glucose homeostasis, and in reduction in body weight by promoting satiety. Actions of GLP-1 are mediated by activation of its receptor GLP-1R, which is widely expressed in several tissues including the retina. The effects of GLP-1R activation are useful in the management of type 2 diabetes mellitus (T2DM). In addition, the activation of GLP-1R has anti-inflammatory effects in several organs, suggesting that it may be also useful in the treatment of inflammatory diseases. Inflammation is a common element in the pathogenesis of several ocular diseases, and the protective effects of treatment with GLP-1 emerged also in retinal diseases. In this review we highlight the anti-inflammatory effects of GLP-1R activation in the retina. Firstly, we summarized the pathogenic role of inflammation in ocular diseases. Then, we described the pleiotropic effects of GLP-1R activation on the cellular components of the retina which are mainly involved in the pathogenesis of inflammatory retinal diseases: the retinal ganglion cells, retinal pigment epithelial cells and endothelial cells.
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Türksever, Cengiz, Lisette T. López Torres, Christophe Valmaggia, and Margarita G. Todorova. "Retinal Oxygenation in Inherited Diseases of the Retina." Genes 12, no. 2 (February 14, 2021): 272. http://dx.doi.org/10.3390/genes12020272.
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(1) Background: The aim of our study was to investigate the relationship between retinal metabolic alterations (retinal vessel oximetry, RO) and structural findings (retinal vessel diameter, central retinal thickness and retinal nerve fiber layer thickness, RNFL) in patients with inherited retinal diseases (IRDs). (2) Methods: A total of 181 eyes of 92 subjects were examined: 121 eyes of 62 patients with IRDs were compared to 60 eyes of 30 healthy age-matched controls. The retinal vessel oximetry was performed with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The oxygen saturation in all four major peripapillary retinal arterioles (A-SO2; %) and venules (V-SO2; %) were measured and their difference (A-V SO2; %) was calculated. Additionally, retinal vessel diameters of the corresponding arterioles (D-A; µm) and venules (D-V; µm) were determined. The peripapillary central retinal thickness and the RNFL thickness were measured using spectral domain optical coherence tomography (SD-OCT) (Carl Zeiss Meditec, Dublin, CA, USA). Moreover, we calculated the mean central retinal oxygen exposure (cO2-E; %/µm) and the mean peripapillary oxygen exposure (pO2-E; %/µm) per micron of central retinal thickness and nerve fiber layer thickness by dividing the mean central retinal thickness (CRT) and the RNFL thickness with the mean A-V SO2. (3) Results: Rod-cone dystrophy patients had the highest V-SO2 and A-SO2, the lowest A-V SO2, the narrowest D-A and D-V and the thickest RNFL, when compared not only to controls (p ≤ 0.040), but also to patients with other IRDs. Furthermore, in rod-cone dystrophies the cO2-E and the pO2-E were higher in comparison to controls and to patients with other IRDs (p ≤ 0.005). Cone-rod dystrophy patients had the lowest cO2-E compared to controls and patients with other IRDs (p ≤ 0.035). Evaluated in central zones, the cO2-E was significantly different when comparing cone-rod dystrophy (CRD) against rod-cone dystrophy (RCD) patients in all zones (p < 0.001), whereas compared with controls and patients with inherited macular dystrophy this was observed only in zones 1 and 2 (p ≤ 0.018). The oxygen exposure was also the highest in the RCD group for both the nasal and the temporal peripapillary area, among all the evaluated groups (p ≤ 0.025). (4) Conclusions: The presented metabolic-structural approach enhances our understanding of inherited photoreceptor degenerations. Clearly demonstrated through the O2-E comparisons, the central and the peripapillary retina in rod-cone dystrophy eyes consume less oxygen than the control-eyes and eyes with other IRDs. Rod-cone dystrophy eyes seem to be proportionally more exposed to oxygen, the later presumably leading to more pronounced oxidative damage-related remodeling.
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Wagner, Natalie, Armin Safaei, Pia A. Vogt, Maurice R. Gammel, H. Burkhard Dick, Sven Schnichels, and Stephanie C. Joachim. "Coculture of ARPE-19 Cells and Porcine Neural Retina as an Ex Vivo Retinal Model." Alternatives to Laboratory Animals 50, no. 1 (January 2022): 27–44. http://dx.doi.org/10.1177/02611929221082662.
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Neural retinal organ cultures are used to investigate ocular pathomechanisms. However, these cultures lack the essential retinal pigment epithelium (RPE) cells, which are part of the actual in vivo retina. To simulate a more realistic ex vivo model, porcine neural retina explants were cocultured with ARPE-19 cells (ARPE-19 group), which are derived from human RPE. To identify whether the entire cells or just the cell factors are necessary, in a second experimental group, porcine neural retina explants were cultured with medium derived from ARPE-19 cells (medium group). Individually cultured neural retina explants served as controls (control group). After 8 days, all neural retinas were analysed to evaluate retinal thickness, photoreceptors, microglia, complement factors and synapses ( n = 6–8 per group). The neural retina thickness in the ARPE-19 group was significantly better preserved than in the control group ( p = 0.031). Also, the number of L-cones was higher in the ARPE-19 group, as compared to the control group ( p < 0.001). Furthermore, the ARPE-19 group displayed an increased presynaptic glutamate uptake (determined via vGluT1 labelling) and enhanced post-synaptic density (determined via PSD-95 labelling). Combined Iba1 and iNOS detection revealed only minor effects of ARPE-19 cells on microglial activity, with a slight downregulation of total microglia activity apparent in the medium group. Likewise, only minor beneficial effects on photoreceptors and synaptic structure were found in the medium group. This novel system offers the opportunity to investigate interactions between the neural retina and RPE cells, and suggests that the inclusion of a RPE feeder layer has beneficial effects on the ex vivo maintenance of neural retina. By modifying the culture conditions, this coculture model allows a better understanding of photoreceptor death and photoreceptor–RPE cell interactions in retinal diseases.
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Ruan, Yue, Tobias Böhmer, Subao Jiang, and Adrian Gericke. "The Role of Adrenoceptors in the Retina." Cells 9, no. 12 (December 3, 2020): 2594. http://dx.doi.org/10.3390/cells9122594.
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The retina is a part of the central nervous system, a thin multilayer with neuronal lamination, responsible for detecting, preprocessing, and sending visual information to the brain. Many retinal diseases are characterized by hemodynamic perturbations and neurodegeneration leading to vision loss and reduced quality of life. Since catecholamines and respective bindings sites have been characterized in the retina, we systematically reviewed the literature with regard to retinal expression, distribution and function of alpha1 (α1)-, alpha2 (α2)-, and beta (β)-adrenoceptors (ARs). Moreover, we discuss the role of the individual adrenoceptors as targets for the treatment of retinal diseases.
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Wang, Jun, Mengling Li, Ziyue Geng, Saadullah Khattak, Xinying Ji, Dongdong Wu, and Yalong Dang. "Role of Oxidative Stress in Retinal Disease and the Early Intervention Strategies: A Review." Oxidative Medicine and Cellular Longevity 2022 (October 14, 2022): 1–13. http://dx.doi.org/10.1155/2022/7836828.
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The retina, owing to its cellular anatomy and physical location, is susceptible to generating reactive oxygen species (ROS), which are associated with several major retinal diseases. When ROS exceeds the body’s natural antioxidants, the retina is in a state of oxidative stress, which is recognized as the pathogenesis of retinal diseases. The early stage of the pathogenic process is an adaptive change in which oxidative stress and endogenous defense mechanisms occur. If no treatment is applied, the retinal diseases will progress to the pathological stage with neuronal and vascular dysfunction or damage and even blindness. This review summarizes the role of oxidative stress in several common retinal diseases, including retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, and retinopathy of prematurity. In addition, we discuss the early intervention strategies for these diseases. An outline is provided to identify potential intervention targets for further research. Early intervention for retinal diseases is necessary and urgent and may offer hope to improve patients’ quality of life through functional vision.
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Kralik, Jakub, and Sonja Kleinlogel. "Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy." International Journal of Molecular Sciences 22, no. 21 (October 26, 2021): 11515. http://dx.doi.org/10.3390/ijms222111515.
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Degenerative diseases of the retina are responsible for the death of photoreceptors and subsequent loss of vision in patients. Nevertheless, the inner retinal layers remain intact over an extended period of time, enabling the restoration of light sensitivity in blind retinas via the expression of optogenetic tools in the remaining retinal cells. The chimeric Opto-mGluR6 protein represents such a tool. With exclusive ON-bipolar cell expression, it combines the light-sensitive domains of melanopsin and the intracellular domains of the metabotropic glutamate receptor 6 (mGluR6), which naturally mediates light responses in these cells. Albeit vision restoration in blind mice by Opto-mGluR6 delivery was previously shown, much is left to be explored in regard to the effects of the timing of the treatment in the degenerated retina. We performed a functional evaluation of Opto-mGluR6-treated murine blind retinas using multi-electrode arrays (MEAs) and observed long-term functional preservation in the treated retinas, as well as successful therapeutical intervention in later stages of degeneration. Moreover, the treatment decreased the inherent retinal hyperactivity of the degenerated retinas to levels undistinguishable from healthy controls. Finally, we observed for the first time micro electroretinograms (mERGs) in optogenetically treated animals, corroborating the origin of Opto-mGluR6 signalling at the level of mGluR6 of ON-bipolar cells.
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Augustin, Albert J., and Jenny Atorf. "The Value of Optical Coherence Tomography Angiography (OCT-A) in Neurological Diseases." Diagnostics 12, no. 2 (February 11, 2022): 468. http://dx.doi.org/10.3390/diagnostics12020468.
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Optical coherence tomography angiography (OCT-A) was commercially introduced in 2014. OCT-A allows a fast, non-invasive, three-dimensional analysis of the retinal vasculature from the vitreoretinal interface to the choriocapillaris. The results can be evaluated separately in automated or custom-defined retinal layers. Since its introduction, OCT-A has also been used in patients with neurological diseases in order to find and characterize retinal biomarkers. Many neurological diseases have retinal manifestations, often preceding the key symptoms of the neurological disease. Anatomically and developmentally, the retina is a part of the brain. In contrast to the brain, the retina is easily accessible for imaging methods; moreover, retinal imaging is more cost-effective than brain imaging. In this review, the current knowledge about OCT-A findings and possible OCT-A biomarkers in neurological diseases is summarized and discussed regarding the value of OCT-A as a diagnostic tool in neurological diseases.
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Sajovic, Jana, Andrej Meglič, Damjan Glavač, Špela Markelj, Marko Hawlina, and Ana Fakin. "The Role of Vitamin A in Retinal Diseases." International Journal of Molecular Sciences 23, no. 3 (January 18, 2022): 1014. http://dx.doi.org/10.3390/ijms23031014.
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Vitamin A is an essential fat-soluble vitamin that occurs in various chemical forms. It is essential for several physiological processes. Either hyper- or hypovitaminosis can be harmful. One of the most important vitamin A functions is its involvement in visual phototransduction, where it serves as the crucial part of photopigment, the first molecule in the process of transforming photons of light into electrical signals. In this process, large quantities of vitamin A in the form of 11-cis-retinal are being isomerized to all-trans-retinal and then quickly recycled back to 11-cis-retinal. Complex machinery of transporters and enzymes is involved in this process (i.e., the visual cycle). Any fault in the machinery may not only reduce the efficiency of visual detection but also cause the accumulation of toxic chemicals in the retina. This review provides a comprehensive overview of diseases that are directly or indirectly connected with vitamin A pathways in the retina. It includes the pathophysiological background and clinical presentation of each disease and summarizes the already existing therapeutic and prospective interventions.
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MELLOUGH, CARLA B., JOSEPH COLLIN, EVELYNE SERNAGOR, NICHOLAS K. WRIDE, DAVID H. W. STEEL, and MAJLINDA LAKO. "Lab generated retina: Realizing the dream." Visual Neuroscience 31, no. 4-5 (May 22, 2014): 317–32. http://dx.doi.org/10.1017/s095252381400008x.
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AbstractBlindness represents an increasing global problem with significant social and economic impact upon affected patients and society as a whole. In Europe, approximately one in 30 individuals experience sight loss and 75% of those are unemployed, a social burden which is very likely to increase as the population of Europe ages. Diseases affecting the retina account for approximately 26% of blindness globally and 70% of blindness in the United Kingdom. To date, there are no treatments to restore lost retinal cells and improve visual function, highlighting an urgent need for new therapeutic approaches. A pioneering breakthrough has demonstrated the ability to generate synthetic retina from pluripotent stem cells under laboratory conditions, a finding with immense relevance for basic research, in vitro disease modeling, drug discovery, and cell replacement therapies. This review summarizes the current achievements in pluripotent stem cell differentiation toward retinal cells and highlights the steps that need to be completed in order to generate human synthetic retinae with high efficiency and reproducibly from patient-specific pluripotent stem cells.
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Ben-Arzi, Assaf, Rita Ehrlich, and Ron Neumann. "Retinal Diseases: The Next Frontier in Pharmacodelivery." Pharmaceutics 14, no. 5 (April 21, 2022): 904. http://dx.doi.org/10.3390/pharmaceutics14050904.
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The future continuous growth of the global older population augments the burden of retinal diseases worldwide. Retinal characteristics isolating and protecting the sensitive neuro-retina from the rest of the ocular tissues challenge drug delivery and promote research and development toward new horizons. In this review, we wish to describe the unmet medical needs, discuss the novel modes of delivery, and disclose to the reader a spectrum of older-to-novel drug delivery technologies, innovations, and the frontier of pharmacodelivery to the retina. Treating the main retinal diseases in the everlasting war against blindness and its associated morbidity has been growing steadily over the last two decades. Implants, new angiogenesis inhibitor agents, micro- and nano-carriers, and the anchored port delivery system are becoming new tools in this war. The revolution and evolution of new delivery methods might be just a few steps ahead, yet its assimilation in our daily clinical work may take time, due to medical, economical, and regulatory elements that need to be met in order to allow successful development and market utilization of new technologies. Therefore, further work is warranted, as detailed in this Pharmaceutics Special Issue.
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Chen, Yingying, Nathan J. Coorey, Meixia Zhang, Shaoxue Zeng, Michele C. Madigan, Xinyuan Zhang, Mark C. Gillies, Ling Zhu, and Ting Zhang. "Metabolism Dysregulation in Retinal Diseases and Related Therapies." Antioxidants 11, no. 5 (May 11, 2022): 942. http://dx.doi.org/10.3390/antiox11050942.
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The human retina, which is part of the central nervous system, has exceptionally high energy demands that requires an efficient metabolism of glucose, lipids, and amino acids. Dysregulation of retinal metabolism disrupts local energy supply and redox balance, contributing to the pathogenesis of diverse retinal diseases, including age-related macular degeneration, diabetic retinopathy, inherited retinal degenerations, and Macular Telangiectasia. A better understanding of the contribution of dysregulated metabolism to retinal diseases may provide better therapeutic targets than we currently have.
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Cabrera DeBuc, Delia, Gabor Mark Somfai, and Akos Koller. "Retinal microvascular network alterations: potential biomarkers of cerebrovascular and neural diseases." American Journal of Physiology-Heart and Circulatory Physiology 312, no. 2 (February 1, 2017): H201—H212. http://dx.doi.org/10.1152/ajpheart.00201.2016.
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Increasing evidence suggests that the conditions of retinal microvessels are indicators to a variety of cerebrovascular, neurodegenerative, psychiatric, and developmental diseases. Thus noninvasive visualization of the human retinal microcirculation offers an exceptional opportunity for the investigation of not only the retinal but also cerebral microvasculature. In this review, we show how the conditions of the retinal microvessels could be used to assess the conditions of brain microvessels because the microvascular network of the retina and brain share, in many aspects, standard features in development, morphology, function, and pathophysiology. Recent techniques and imaging modalities, such as optical coherence tomography (OCT), allow more precise visualization of various layers of the retina and its microcirculation, providing a “microscope” to brain microvessels. We also review the potential role of retinal microvessels in the risk identification of cerebrovascular and neurodegenerative diseases. The association between vision problems and cerebrovascular and neurodegenerative diseases, as well as the possible role of retinal microvascular imaging biomarkers in cerebrovascular and neurodegenerative screening, their potentials, and limitations, are also discussed.
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Gardner, Michael, Nitesh Katta, Ayesha Rahman, Henry Rylander, and Thomas Milner. "Design Considerations for Murine Retinal Imaging Using Scattering Angle Resolved Optical Coherence Tomography." Applied Sciences 8, no. 11 (November 5, 2018): 2159. http://dx.doi.org/10.3390/app8112159.
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Optical coherence tomography (OCT), an optical imaging approach enabling cross-sectional analysis of turbid samples, is routinely used for retinal imaging in human and animal models of diseases affecting the retina. Scattering angle resolved (SAR-)OCT has previously been demonstrated as offering additional contrast in human studies, but no SAR-OCT system has been reported in detail for imaging the retinas of mice. An optical model of a mouse eye was designed and extended for validity at wavelengths of light around 1310 nm; this model was then utilized to develop a SAR-OCT design for murine retinal imaging. A Monte Carlo technique simulates light scattering from the retina, and the simulation results are confirmed with SAR-OCT images. Various images from the SAR-OCT system are presented and utility of the system is described. SAR-OCT is demonstrated as a viable and robust imaging platform to extend utility of retinal OCT imaging by incorporating scattering data into investigative ophthalmologic analysis.
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Nakagami, Yasuhiro. "Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases." Oxidative Medicine and Cellular Longevity 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/7469326.
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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many species. The retina is constantly exposed to reactive oxygen species, and oxidative stress is a major contributor to age-related macular diseases. Moreover, the resulting inflammation and neuronal degeneration are also related to other retinal diseases. The well-known Nrf2 activators, bardoxolone methyl and its derivatives, have been the subject of a number of clinical trials, including those aimed at treating chronic kidney disease, pulmonary arterial hypertension, and mitochondrial myopathies. Recent studies suggest that Nrf2 activation protects the retina from retinal diseases. In particular, this is supported by the finding that Nrf2 knockout mice display age-related retinal degeneration. Moreover, the concept has been validated by the efficacy of Nrf2 activators in a number of retinal pathological models. We have also recently succeeded in generating a novel Nrf2 activator, RS9, using a biotransformation technique. This review discusses current links between retinal diseases and Nrf2 and the possibility of treating retinal diseases by activating the Nrf2 signaling pathway.
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Nwagbo, Uzoamaka, and Paul S. Bernstein. "Understanding the Roles of Very-Long-Chain Polyunsaturated Fatty Acids (VLC-PUFAs) in Eye Health." Nutrients 15, no. 14 (July 10, 2023): 3096. http://dx.doi.org/10.3390/nu15143096.
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Lipids serve many roles in the neural system, from synaptic stabilization and signaling to DNA regulation and neuroprotection. They also regulate inflammatory responses, maintain cellular membrane structure, and regulate the homeostatic balance of ions and signaling molecules. An imbalance of lipid subgroups is implicated in the progression of many retinal diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, and diet can play a key role in influencing these diseases’ onset, progression, and severity. A special class of lipids termed very-long-chain polyunsaturated fatty acids (VLC-PUFAs) is found exclusively in mammalian vertebrate retinas and a few other tissues. They comprise <2% of fatty acids in the retina and are depleted in the retinas of patients with diseases like diabetic retinopathy and AMD. However, the implications of the reduction in VLC-PUFA levels are poorly understood. Dietary supplementation studies and ELOVL4 transgene studies have had positive outcomes. However, much remains to be understood about their role in retinal health and the potential for targeted therapies against retinal disease.
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Hou, Xiao-Wen, Ying Wang, Chao-Fu Ke, Mei-Yan Li, and Chen-Wei Pan. "Metabolomics and Biomarkers in Retinal and Choroidal Vascular Diseases." Metabolites 12, no. 9 (August 30, 2022): 814. http://dx.doi.org/10.3390/metabo12090814.
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The retina is one of the most important structures in the eye, and the vascular health of the retina and choroid is critical to visual function. Metabolomics provides an analytical approach to endogenous small molecule metabolites in organisms, summarizes the results of “gene-environment interactions”, and is an ideal analytical tool to obtain “biomarkers” related to disease information. This study discusses the metabolic changes in neovascular diseases involving the retina and discusses the progress of the study from the perspective of metabolomics design and analysis. This study advocates a comparative strategy based on existing studies, which encompasses optimization of the performance of newly identified biomarkers and the consideration of the basis of existing studies, which facilitates quality control of newly discovered biomarkers and is recommended as an additional reference strategy for new biomarker discovery. Finally, by describing the metabolic mechanisms of retinal and choroidal neovascularization, based on the results of existing studies, this study provides potential opportunities to find new therapeutic approaches.
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Yu, Dao-Yi, and Stephen J. Cringle. "Low oxygen consumption in the inner retina of the visual streak of the rabbit." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 1 (January 2004): H419—H423. http://dx.doi.org/10.1152/ajpheart.00643.2003.
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The oxygen requirements of different retinal layers are of interest in understanding the vulnerability of the retina to hypoxic damage in retinal diseases with an ischemic component. Here, we report the first measurements of retinal oxygen consumption in the visual streak of the rabbit retina, the region with the highest density of retinal neurons, and compare it with that in the less-specialized region of the retina underlying the vascularized portion of the rabbit retina. Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of retinal depth in anesthetized animals. Measurements were performed in the region of the retina containing overlying retinal vessels and in the center of the visual streak. Established mathematical analyses of the intraretinal oxygen distribution were used to quantify the rate of oxygen consumption in the inner and outer retina and the relative oxygen contributions from the choroidal and vitreal sides. Outer retinal oxygen consumption was higher in the visual streak than in the vascularized area (means ± SE, 284 ± 20 vs. 210 ± 23 nl O2·min–1·cm–2, P = 0.026, n = 10). However, inner retinal oxygen consumption in the visual streak was significantly lower than in the vascular area (57 ± 4.3 vs. 146 ± 12 nl O2·min–1·cm–2, P < 0.001). We conclude that despite the higher processing requirements of the inner retina in the visual streak, it has a significantly lower oxygen consumption rate than the inner retina underlying the retinal vasculature. This suggests that the oxygen uptake of the inner retina is regulated to a large degree by the available oxygen supply rather than the processing requirements of the inner retina alone.
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Romero, Francisco J., Manuel Diaz-Llopis, M. Inmaculada Romero-Gomez, Maria Miranda, Rebeca Romero-Wenz, Javier Sancho-Pelluz, Belén Romero, Maria Muriach, and Jorge M. Barcia. "Small Extracellular Vesicles and Oxidative Pathophysiological Mechanisms in Retinal Degenerative Diseases." International Journal of Molecular Sciences 25, no. 3 (January 28, 2024): 1618. http://dx.doi.org/10.3390/ijms25031618.
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This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles’ cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.
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García-Ayuso, Diego, Johnny Di Pierdomenico, Manuel Vidal-Sanz, and María P. Villegas-Pérez. "Retinal Ganglion Cell Death as a Late Remodeling Effect of Photoreceptor Degeneration." International Journal of Molecular Sciences 20, no. 18 (September 19, 2019): 4649. http://dx.doi.org/10.3390/ijms20184649.
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Inherited or acquired photoreceptor degenerations, one of the leading causes of irreversible blindness in the world, are a group of retinal disorders that initially affect rods and cones, situated in the outer retina. For many years it was assumed that these diseases did not spread to the inner retina. However, it is now known that photoreceptor loss leads to an unavoidable chain of events that cause neurovascular changes in the retina including migration of retinal pigment epithelium cells, formation of “subretinal vascular complexes”, vessel displacement, retinal ganglion cell (RGC) axonal strangulation by retinal vessels, axonal transport alteration and, ultimately, RGC death. These events are common to all photoreceptor degenerations regardless of the initial trigger and thus threaten the outcome of photoreceptor substitution as a therapeutic approach, because with a degenerating inner retina, the photoreceptor signal will not reach the brain. In conclusion, therapies should be applied early in the course of photoreceptor degeneration, before the remodeling process reaches the inner retina.
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D'Amico, Donald J. "Diseases of the Retina." New England Journal of Medicine 331, no. 2 (July 14, 1994): 95–106. http://dx.doi.org/10.1056/nejm199407143310207.
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Gofas-Salas, Elena, Nathaniel Norberg, Céline Louapre, Ysoline Beigneux, Catherine Vignal Clermont, Michel Paques, and Kate Grieve. "Phase contrast imaging to detect transparent cells in the retinal ganglion cells layer." EPJ Web of Conferences 266 (2022): 04003. http://dx.doi.org/10.1051/epjconf/202226604003.
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The eye is an optical window giving access to neural networks in a non-invasive way. It is possible to find in the retina biomarkers informing about the pathological state of other parts of the human body, and in particular of the brain. Neurodegenerative diseases could thus be diagnosed early and monitored by high-resolution imaging of the retina. However, a large part of the neurons in the retina are too transparent to be detected by existing techniques. At the Quinze-Vingts hospital, we have a unique retinal imaging platform in which ophthalmologists, neurologists and engineers participate. We implemented a technique based on scanning laser ophthalmoscopy (SLO) to capture the fine variations in refractive index between retinal cells. In this project we aimed at imaging and monitor cellular changes on transparent cells in the retinal ganglion cells layer in vivo on healthy participants and patients with neurodegenerative diseases.
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Lee, Deokho, Heonuk Jeong, Yukihiro Miwa, Ari Shinojima, Yusaku Katada, Kazuo Tsubota, and Toshihide Kurihara. "Retinal dysfunction induced in a mouse model of unilateral common carotid artery occlusion." PeerJ 9 (June 21, 2021): e11665. http://dx.doi.org/10.7717/peerj.11665.
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Background Retinal ischemic stresses are associated with the pathogenesis of various retinal vascular diseases. To investigate pathological mechanisms of retinal ischemia, reproducible, robust and clinically significant experimental rodent models are highly needed. Previously, we established a stable murine model of chronic hypoperfusion retinal injuries by permanent unilateral common carotid artery occlusion (UCCAO) and demonstrated chronic pathological processes in the ischemic retina after the occlusion; however, retinal functional deficits and other acute retinal ischemic injuries by UCCAO still remain obscure. In this study, we attempted to examine retinal functional changes as well as acute retinal ischemic alterations such as retinal thinning, gliosis and cell death after UCCAO. Methods Adult mice (male C57BL/6, 6–8 weeks old) were subjected to UCCAO in the right side, and retinal function was primarily measured using electroretinography for 14 days after the surgery. Furthermore, retinal thinning, gliosis and cell death were investigated using optical coherence tomography, immunohistochemistry and TUNEL assay, respectively. Results Functional deficits in the unilateral right retina started to be seen 7 days after the occlusion. Specifically, the amplitude of b-wave dramatically decreased while that of a-wave was slightly affected. 14 days after the occlusion, the amplitudes of both waves and oscillatory potentials were significantly detected decreased in the unilateral right retina. Even though a change in retinal thickness was not dramatically observed among all the eyes, retinal gliosis and cell death in the unilateral right retina were substantially observed after UCCAO. Conclusions Along with previous retinal ischemic results in this model, UCCAO can stimulate retinal ischemia leading to functional, morphological and molecular changes in the retina. This model can be useful for the investigation of pathological mechanisms for human ischemic retinopathies and furthermore can be utilized to test new drugs for various ischemic ocular diseases.
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DOU, PENG, YANG ZHANG, RUI ZHENG, YU YE, JIANBO MAO, LEI LIU, MING WU, and MINGZHAI SUN. "RETINAL IMAGING AND ANALYSIS USING MACHINE LEARNING WITH INFORMATION FUSION OF THE FUNCTIONAL AND STRUCTURAL FEATURES BASED ON A DUAL-MODAL FUNDUS CAMERA." Journal of Mechanics in Medicine and Biology 21, no. 06 (June 2, 2021): 2150030. http://dx.doi.org/10.1142/s0219519421500305.
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Retinal diseases and systemic diseases, such as diabetic retinopathy (DR) and Alzheimer’s disease, may manifest themselves in the retina, changing the retinal oxygen saturation ([Formula: see text]) level or the retinal vascular structures. Recent studies explored the correlation of diseases with either retina vascular structures or [Formula: see text] level, but not both due to the lack of proper instrument or methodology. In this study, we applied a dual-modal fundus camera and developed a deep learning-based analysis method to simultaneously acquire and quantify the [Formula: see text] and vascular structures. Deep learning was used to automatically locate the optic discs and segment arterioles and venules of the blood vessels. We then sought to apply machine learning methods, such as random forest (RF) and support vector machine (SVM), to fuse the [Formula: see text] level and retinal vessel parameters as different features to discriminate against the disease from the healthy controls. We showed that the fusion of the functional (oxygen saturation) and structural (vascular parameters) features offers better performance to classify diseased and healthy subjects. For example, we gained a 13.8% and 2.0% increase in the accuracy with fusion using the RF and SVM to classify the nonproliferative DR and the healthy controls.
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Jaroszynska, Natalia, Philippa Harding, and Mariya Moosajee. "Metabolism in the Zebrafish Retina." Journal of Developmental Biology 9, no. 1 (March 15, 2021): 10. http://dx.doi.org/10.3390/jdb9010010.
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Retinal photoreceptors are amongst the most metabolically active cells in the body, consuming more glucose as a metabolic substrate than even the brain. This ensures that there is sufficient energy to establish and maintain photoreceptor functions during and after their differentiation. Such high dependence on glucose metabolism is conserved across vertebrates, including zebrafish from early larval through to adult retinal stages. As the zebrafish retina develops rapidly, reaching an adult-like structure by 72 hours post fertilisation, zebrafish larvae can be used to study metabolism not only during retinogenesis, but also in functionally mature retinae. The interplay between rod and cone photoreceptors and the neighbouring retinal pigment epithelium (RPE) cells establishes a metabolic ecosystem that provides essential control of their individual functions, overall maintaining healthy vision. The RPE facilitates efficient supply of glucose from the choroidal vasculature to the photoreceptors, which produce metabolic products that in turn fuel RPE metabolism. Many inherited retinal diseases (IRDs) result in photoreceptor degeneration, either directly arising from photoreceptor-specific mutations or secondary to RPE loss, leading to sight loss. Evidence from a number of vertebrate studies suggests that the imbalance of the metabolic ecosystem in the outer retina contributes to metabolic failure and disease pathogenesis. The use of larval zebrafish mutants with disease-specific mutations that mirror those seen in human patients allows us to uncover mechanisms of such dysregulation and disease pathology with progression from embryonic to adult stages, as well as providing a means of testing novel therapeutic approaches.
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Ong, Joshua, Arman Zarnegar, Giulia Corradetti, Sumit Randhir Singh, and Jay Chhablani. "Advances in Optical Coherence Tomography Imaging Technology and Techniques for Choroidal and Retinal Disorders." Journal of Clinical Medicine 11, no. 17 (August 31, 2022): 5139. http://dx.doi.org/10.3390/jcm11175139.
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Optical coherence tomography (OCT) imaging has played a pivotal role in the field of retina. This light-based, non-invasive imaging modality provides high-quality, cross-sectional analysis of the retina and has revolutionized the diagnosis and management of retinal and choroidal diseases. Since its introduction in the early 1990s, OCT technology has continued to advance to provide quicker acquisition times and higher resolution. In this manuscript, we discuss some of the most recent advances in OCT technology and techniques for choroidal and retinal diseases. The emerging innovations discussed include wide-field OCT, adaptive optics OCT, polarization sensitive OCT, full-field OCT, hand-held OCT, intraoperative OCT, at-home OCT, and more. The applications of these rising OCT systems and techniques will allow for a closer monitoring of chorioretinal diseases and treatment response, more robust analysis in basic science research, and further insights into surgical management. In addition, these innovations to optimize visualization of the choroid and retina offer a promising future for advancing our understanding of the pathophysiology of chorioretinal diseases.
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Zueva, M. V., N. V. Neroeva, L. A. Katargina, A. N. Zhuravleva, V. I. Kotelin, I. V. Tsapenko, and D. V. Fadeev. "Modifying treatment of degenerative retinal diseases. Part 1. Adaptive and non-adaptive retinal plasticity." Russian Ophthalmological Journal 16, no. 2 (July 2, 2023): 160–65. http://dx.doi.org/10.21516/2072-0076-2023-16-2-160-165.
Full textAbstract:
Retinal structural plasticity is manifested in multiple damages of the retina. In many cases, the response to these damages is identical at both the cellular and molecular levels, involves similar sets of cellular signals, and is associated with a change in the structure of the retina and remodeling of the neural connections. The review discusses the common and specific features of adaptive and non-adaptive retinal plasticity, which characterize glaucoma, age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and retinopathy of prematurity. Given the common features of neurodegeneration and retinal plasticity in brain and retinal diseases, similar therapeutic strategies can be used in many cases to preserve the structure connectivity and retinal function, which stop or slow down the clinical evolution of the disease by either suppressing primary events or enhancing compensatory and regenerative mechanisms in the nervous tissue. Part 2 of the review will present neuroplasticity-based modifying therapy methods for retinal degenerative diseases.
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Alves, C. Henrique, Rosa Fernandes, Ana Raquel Santiago, and António Francisco Ambrósio. "Microglia Contribution to the Regulation of the Retinal and Choroidal Vasculature in Age-Related Macular Degeneration." Cells 9, no. 5 (May 14, 2020): 1217. http://dx.doi.org/10.3390/cells9051217.
Full textAbstract:
The retina is a highly metabolically active tissue with high-level consumption of nutrients and oxygen. This high metabolic demand requires a properly developed and maintained vascular system. The retina is nourished by two systems: the central retinal artery that supplies the inner retina and the choriocapillaris that supplies the outer retina and retinal pigment epithelium (RPE). Pathological neovascularization, characterized by endothelial cell proliferation and new vessel formation, is a common hallmark in several retinal degenerative diseases, including age-related macular degeneration (AMD). A limited number of studies have suggested that microglia, the resident immune cells of the retina, have an important role not only in the pathology but also in the formation and physiology of the retinal vascular system. Here, we review the current knowledge on microglial interaction with the retinal vascular system under physiological and pathological conditions. To do so, we first highlight the role of microglial cells in the formation and maintenance of the retinal vasculature system. Thereafter, we discuss the molecular signaling mechanisms through which microglial cells contribute to the alterations in retinal and choroidal vasculatures and to the neovascularization in AMD.
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Sharma, Anamika, and Nikhlesh K. Singh. "Long Non-Coding RNAs and Proliferative Retinal Diseases." Pharmaceutics 15, no. 5 (May 10, 2023): 1454. http://dx.doi.org/10.3390/pharmaceutics15051454.
Full textAbstract:
Retinopathy refers to disorders that affect the retina of the eye, which are frequently caused by damage to the retina’s vascular system. This causes leakage, proliferation, or overgrowth of blood vessels through the retina, which can lead to retinal detachment or breakdown, resulting in vision loss and, in rare cases, blindness. In recent years, high-throughput sequencing has significantly hastened the discovery of new long non-coding RNAs (lncRNAs) and their biological functions. LncRNAs are rapidly becoming recognized as critical regulators of several key biological processes. Current breakthroughs in bioinformatics have resulted in the identification of several lncRNAs that may have a role in retinal disorders. Nevertheless, mechanistic investigations have yet to reveal the relevance of these lncRNAs in retinal disorders. Using lncRNA transcripts for diagnostic and/or therapeutic purposes may aid in the development of appropriate treatment regimens and long-term benefits for patients, as traditional medicines and antibody therapy only provide temporary benefits that must be repeated. In contrast, gene-based therapies can provide tailored, long-term treatment solutions. Here, we will discuss how different lncRNAs affect different retinopathies, including age-related macular degeneration (AMD), diabetic retinopathy (DR), central retinal vein occlusion (CRVO), proliferative vitreoretinopathy (PVR), and retinopathy of prematurity (ROP), which can cause visual impairment and blindness, and how these retinopathies can be identified and treated using lncRNAs.
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Lenin, Raji, Samuel M. Thomas, and Rajashekhar Gangaraju. "Endothelial Activation and Oxidative Stress in Neurovascular Defects of the Retina." Current Pharmaceutical Design 24, no. 40 (March 15, 2019): 4742–54. http://dx.doi.org/10.2174/1381612825666190115122622.
Full textAbstract:
Background: The eye is considered as a window of the disease, and a better understanding of neurodegenerative changes in the eye may help diagnose and manage neurodegenerative diseases including the diseases of brain, heart, kidney and liver. In the eye, the blood retinal barrier (BRB] is maintained by a combination of endothelial cells, pericytes, and glia. This BRB integrity is fundamental to the physiology of retinal cellular function and accurate vision. The role of endothelial dysfunction as a consequence of endothelial activation in the initiation and prolongation of neurovascular diseases of the retina is emerging. Methods: The observations made in this article are a result of our research over the years in the subject matter and also based on a literature search using PubMed with keywords including but not limited to endothelial, permeability, oxidative stress, ROS, TNF-α, retina, injury, and neurodegeneration. Several studies were identified that fulfilled the inclusion criteria. Overall, published studies support an association between endothelial activation, inflammation and oxidative stress in retinal diseases. Although the selection of specific endothelial activation biomarkers in the retina is less clear, there is an increased association between inflammation in the severity of diabetic retinopathy. Studies in other clinically relevant studies demonstrated a strong association of endothelial activation to alterations in mitochondrial respiratory chain complexes, pericyte integrity, microglial activation, neutrophil extracellular traps and elevated plasma concentrations of TNF-α. Conclusion: The compromise in BRB as a consequence of the neurovascular unit in the retinal tissue has gained a lot of attention and studies addressing these should result in a better understanding of the pathophysiology of retinal diseases. Although there are no specific retinal markers of endothelial activation and inflammation, future studies using specific models that display endothelial activation, inflammation and oxidative stress likely yield better understanding on the cause or effect relationship of endothelial activation in retinal diseases.