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1

Kuznetsova, Alla V., Alexander M. Kurinov, and Maria A. Aleksandrova. "Cell Models to Study Regulation of Cell Transformation in Pathologies of Retinal Pigment Epithelium." Journal of Ophthalmology 2014 (2014): 1–18. http://dx.doi.org/10.1155/2014/801787.

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The retinal pigment epithelium (RPE) plays a key role in the development of many eye diseases leading to visual impairment and even blindness. Cell culture models of pathological changes in the RPE make it possible to study factors responsible for these changes and signaling pathways coordinating cellular and molecular mechanisms of cell interactions under pathological conditions. Moreover, they give an opportunity to reveal target cells and develop effective specific treatment for degenerative and dystrophic diseases of the retina. In this review, data are presented on RPE cell sources for cu
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2

Marrs, J. A., C. Andersson-Fisone, M. C. Jeong, et al. "Plasticity in epithelial cell phenotype: modulation by expression of different cadherin cell adhesion molecules." Journal of Cell Biology 129, no. 2 (1995): 507–19. http://dx.doi.org/10.1083/jcb.129.2.507.

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A primary function of cadherins is to regulate cell adhesion. Here, we demonstrate a broader function of cadherins in the differentiation of specialized epithelial cell phenotypes. In situ, the rat retinal pigment epithelium (RPE) forms cell-cell contacts within its monolayer, and at the apical membrane with the neural retina; Na+, K(+)-ATPase and the membrane cytoskeleton are restricted to the apical membrane. In vitro, RPE cells (RPE-J cell line) express an endogenous cadherin, form adherens junctions and a tight monolayer, but Na+,K(+)-ATPase is localized to both apical and basal-lateral me
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3

Zhou, Liangliang, Ya Mo, Haiyan Zhang, Mengdi Zhang, Jiayu Xu, and Sumin Liang. "Role of AMPK-regulated autophagy in retinal pigment epithelial cell homeostasis: A review." Medicine 103, no. 28 (2024): e38908. http://dx.doi.org/10.1097/md.0000000000038908.

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The retinal pigment epithelium (RPE) is a regularly arranged monolayer of cells in the outermost layer of the retina. It is crucial for transporting nutrients and metabolic substances in the retina and maintaining the retinal barrier. RPE dysfunction causes diseases related to vision loss. Thus, understanding the mechanisms involved in normal RPE function is vital. Adenosine monophosphate-activated protein kinase (AMPK) is an RPE energy sensor regulating various signaling and metabolic pathways to maintain cellular energetic homeostasis. AMPK activation is involved in multiple signaling pathwa
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Voisin, Audrey, Christelle Monville, Alexandra Plancheron, Emile Béré, Afsaneh Gaillard, and Nicolas Leveziel. "Cathepsin B pH-Dependent Activity Is Involved in Lysosomal Dysregulation in Atrophic Age-Related Macular Degeneration." Oxidative Medicine and Cellular Longevity 2019 (December 6, 2019): 1–15. http://dx.doi.org/10.1155/2019/5637075.

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Age-related macular degeneration (AMD) is characterized by retinal pigment epithelial (RPE) cell dysfunction beginning at early stages of the disease. The lack of an appropriate in vitro model is a major limitation in understanding the mechanisms leading to the occurrence of AMD. This study compared human-induced pluripotent stem cell- (hiPSC-) RPE cells derived from atrophic AMD patients (77 y/o±7) to hiPSC-RPE cells derived from healthy elderly individuals with no drusen or pigmentary alteration (62.5 y/o±17.5). Control and AMD hiPSC-RPE cell lines were characterized by immunofluorescence, f
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5

Kindzelskii, Andrei L., Victor M. Elner, Susan G. Elner, Dongli Yang, Bret A. Hughes, and Howard R. Petty. "Toll-Like Receptor 4 (TLR4) of Retinal Pigment Epithelial Cells Participates in Transmembrane Signaling in Response to Photoreceptor Outer Segments." Journal of General Physiology 124, no. 2 (2004): 139–49. http://dx.doi.org/10.1085/jgp.200409062.

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Retinal pigment epithelial (RPE) cells mediate the recognition and clearance of effete photoreceptor outer segments (POS), a process central to the maintenance of normal vision. Given the emerging importance of Toll-like receptors (TLRs) in transmembrane signaling in response to invading pathogens as well as endogenous substances, we hypothesized that TLRs are associated with RPE cell management of POS. TLR4 clusters on human RPE cells in response to human, but not bovine, POS. However, TLR4 clustering could be inhibited by saturating concentrations of an inhibitory anti-TLR4 mAb. Furthermore,
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6

Szatmári-Tóth, Mária, Tanja Ilmarinen, Alexandra Mikhailova, et al. "Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium-Role in Dead Cell Clearance and Inflammation." International Journal of Molecular Sciences 20, no. 4 (2019): 926. http://dx.doi.org/10.3390/ijms20040926.

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Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional phagocytes can result in debris formation and development of age-related macular degeneration (AMD). Chronic oxidative stress and inflammation play an important role in AMD pathogenesis. Only a few well-established in vitro phagocytosis assay models exist. We propose human embryonic stem cell-derived-RPE cells as a new model for studying RPE cell removal by professional phagocytes. The characteristics of human embryonic stem cells-derived RPE (hESC-RPE) are similar to native RPEs based on their gene and protein
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7

Daniele, Elena, Lorenzo Bosio, Noor Ahmed Hussain, et al. "Denuded Descemet’s membrane supports human embryonic stem cell-derived retinal pigment epithelial cell culture." PLOS ONE 18, no. 2 (2023): e0281404. http://dx.doi.org/10.1371/journal.pone.0281404.

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Recent clinical studies suggest that retinal pigment epithelial (RPE) cell replacement therapy may preserve vision in retinal degenerative diseases. Scaffold-based methods are being tested in ongoing clinical trials for delivering pluripotent-derived RPE cells to the back of the eye. The aim of this study was to investigate human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells survival and behaviour on a decellularized Descemet’s Membrane (DM), which may be of clinical relevance in retinal transplantation. DMs were isolated from human donor corneas and treated with ther
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8

Hellinen, Laura, Heidi Hongisto, Eva Ramsay, et al. "Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery." Pharmaceutics 12, no. 2 (2020): 176. http://dx.doi.org/10.3390/pharmaceutics12020176.

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The retinal pigment epithelial (RPE) cell monolayer forms the outer blood–retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of several RPE secondary cell lines (ARPE19, ARPE19mel, and LEPI) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexa
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9

Kamao, Hiroyuki, Atsushi Miki, and Junichi Kiryu. "ROCK Inhibitor-Induced Promotion of Retinal Pigment Epithelial Cell Motility during Wound Healing." Journal of Ophthalmology 2019 (June 19, 2019): 1–10. http://dx.doi.org/10.1155/2019/9428738.

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Purpose. No standard therapy for RPE tear, a complication of neovascular age-related macular degeneration, exists even though RPE tears cause severe vision loss, and promotion of cell proliferation and/or migration could be a candidate RPE tear therapy. The aim of this study is to evaluate the effect of Rho-associated coiled-coil containing kinase (ROCK) inhibitor Y27632 on retinal pigment epithelial (RPE) cell motility during wound healing. Methods. Human RPE cells were cultured in media with and without 10 μM Y27632. A luminescent cell viability assay and vinculin immunocytochemistry were us
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10

Bhattacharya, Sujoy, Tzushan Sharon Yang, Bretton P. Nabit, Evan S. Krystofiak, Tonia S. Rex, and Edward Chaum. "Prominin-1 Knockdown Causes RPE Degeneration in a Mouse Model." Cells 13, no. 21 (2024): 1761. http://dx.doi.org/10.3390/cells13211761.

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There are currently no effective treatments for retinal pigment epithelial (RPE) cell loss in atrophic AMD (aAMD). However, our research on Prominin-1 (Prom1), a known structural protein in photoreceptors (PRs), has revealed its distinct role in RPE and offers promising insights. While pathogenic Prom1 mutations have been linked to macular diseases with RPE atrophy, the broader physiological impact of dysfunctional Prom1 in RPE loss is unclear. We have shown that Prom1 plays a crucial role in regulating autophagy and cellular homeostasis in human and mouse RPE (mRPE) cells in vitro. Neverthele
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11

Arai, Rei, Ayumi Usui-Ouchi, Yosuke Ito, Keitaro Mashimo, Akira Murakami, and Nobuyuki Ebihara. "Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells: Focus on Mast Cell Tryptase." Mediators of Inflammation 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/3124753.

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Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influenc
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12

Raeker, Maide Ö., Nirosha D. Perera, Athanasios J. Karoukis, et al. "Reduced Retinal Pigment Epithelial Autophagy Due to Loss of Rab12 Prenylation in a Human iPSC-RPE Model of Choroideremia." Cells 13, no. 12 (2024): 1068. http://dx.doi.org/10.3390/cells13121068.

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Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in CHM, encoding Rab escort protein 1 (REP-1), leading to under-prenylation of Rab GTPases (Rabs). Despite ubiquitous expression of CHM, the phenotype is limited to degeneration of the retina, retinal pigment epithelium (RPE), and choroid, with evidence for primary pathology in RPE cells. However, the spectrum of under-prenylated Rabs in RPE cells and how they contribute to RPE dysfunction remain unknown. A CRISPR/Cas-9-edited CHM−/− iPSC-RPE model was generated with isogenic control cells. Unprenylated Rabs were biotinyl
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13

Gupta, Santosh, Lyubomyr Lytvynchuk, Taras Ardan, et al. "Retinal Pigment Epithelium Cell Development: Extrapolating Basic Biology to Stem Cell Research." Biomedicines 11, no. 2 (2023): 310. http://dx.doi.org/10.3390/biomedicines11020310.

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The retinal pigment epithelium (RPE) forms an important cellular monolayer, which contributes to the normal physiology of the eye. Damage to the RPE leads to the development of degenerative diseases, such as age-related macular degeneration (AMD). Apart from acting as a physical barrier between the retina and choroidal blood vessels, the RPE is crucial in maintaining photoreceptor (PR) and visual functions. Current clinical intervention to treat early stages of AMD includes stem cell-derived RPE transplantation, which is still in its early stages of evolution. Therefore, it becomes essential t
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14

Pandey, Ravi S., Mark P. Krebs, Mohan T. Bolisetty, et al. "Single-Cell RNA Sequencing Reveals Molecular Features of Heterogeneity in the Murine Retinal Pigment Epithelium." International Journal of Molecular Sciences 23, no. 18 (2022): 10419. http://dx.doi.org/10.3390/ijms231810419.

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Transcriptomic analysis of the mammalian retinal pigment epithelium (RPE) aims to identify cellular networks that influence ocular development, maintenance, function, and disease. However, available evidence points to RPE cell heterogeneity within native tissue, which adds complexity to global transcriptomic analysis. Here, to assess cell heterogeneity, we performed single-cell RNA sequencing of RPE cells from two young adult male C57BL/6J mice. Following quality control to ensure robust transcript identification limited to cell singlets, we detected 13,858 transcripts among 2667 and 2846 RPE
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15

Kamao, Hiroyuki, Atsushi Miki, and Junichi Kiryu. "Evaluation of Retinal Pigment Epithelial Cell Cytotoxicity of Recombinant Tissue Plasminogen Activator Using Human-Induced Pluripotent Stem Cells." Journal of Ophthalmology 2019 (March 19, 2019): 1–10. http://dx.doi.org/10.1155/2019/7189241.

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Purpose. The evaluation of drug-induced cytotoxicity is of great importance for the clinical application of pharmaceutical products, and human-induced pluripotent stem cells (hiPSCs) have received considerable scrutiny as a cell source for in vitro cytotoxicity testing. The aim of this study is to validate the concept of cytotoxicity testing using hiPSC-derived retinal pigment epithelium (hiPSC-RPE) by comparing the responsiveness of human fetal RPE (hfRPE) and human RPE cell line (ARPE19) to recombinant tissue plasminogen activator (rtPA). Methods. HfRPE, two types of hiPSC-RPE, and ARPE19 we
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16

Du, Jianhai, Aya Yanagida, Kaitlen Knight, et al. "Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium." Proceedings of the National Academy of Sciences 113, no. 51 (2016): 14710–15. http://dx.doi.org/10.1073/pnas.1604572113.

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The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using13C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line. Loss of reduc
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17

Kalnins, Vitauts I., Martin Sandig, Greg J. Hergott, and Haruhiko Nagai. "Microfilament organization and wound repair in retinal pigment epithelium." Biochemistry and Cell Biology 73, no. 9-10 (1995): 709–22. http://dx.doi.org/10.1139/o95-079.

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Several systems of microfilaments (MF) associated with adherens-type junctions between adjacent retinal pigment epithelial (RPE) cells and between these cells and the substratum play an important role in maintaining the integrity and organization of the RPE. They include prominent, contractile circumferential MF bundles that are associated with the zonula adherens (ZA) junctions. In chick RPE, these junctions are assembled from smaller subunits thus giving greater structural flexibility to the junctional region. Because the separation of the junctions requires trypsin and low calcium, both cal
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18

Yang, Chao, Lijun Ge, Xiyong Yu, Philip Lazarovici, and Wenhua Zheng. "Artemisinin Confers Cytoprotection toward Hydrogen Peroxide-Induced Cell Apoptosis in Retinal Pigment Epithelial Cells in Correlation with the Increased Acetylation of Histone H4 at Lysine 8." Molecules 29, no. 8 (2024): 1789. http://dx.doi.org/10.3390/molecules29081789.

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Increased oxidative stress is one of the critical pathologies inducing age-related macular degeneration (AMD), characterized by retinal pigment epithelial (RPE) cell damage and death. The unbalanced acetylation and deacetylation of histones have been implicated in AMD pathogenesis or hydrogen peroxide (H2O2)-induced cell damage. Therefore, strategies aimed at controlling the balance between acetylation and deacetylation may effectively protect RPE cells from oxidative damage. Artemisinin is an antimalarial lactone drug derived from Artemisia annua, with antioxidant activity known to modulate h
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19

Vinores, S. A., R. McGehee, A. Lee, C. Gadegbeku, and P. A. Campochiaro. "Ultrastructural localization of blood-retinal barrier breakdown in diabetic and galactosemic rats." Journal of Histochemistry & Cytochemistry 38, no. 9 (1990): 1341–52. http://dx.doi.org/10.1177/38.9.2117624.

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Breakdown of the blood-retinal barrier (BRB) is an early event in diabetic and galactosemic rats, but the location and nature of the specific defect(s) are controversial. Using an electron microscopic immunocytochemical technique, the retinas of normal, diabetic, and galactosemic rats were immunostained for endogenous albumin. Normal rats showed little evidence of BRB breakdown at either the inner barrier (retinal vasculature) or the outer barrier (retinal pigment epithelium) (RPE). In diabetic and galactosemic rats, as was true in human diabetics, BRB breakdown occurred predominantly at the i
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20

Troutt, L. L., and B. Burnside. "The unusual microtubule polarity in teleost retinal pigment epithelial cells." Journal of Cell Biology 107, no. 4 (1988): 1461–64. http://dx.doi.org/10.1083/jcb.107.4.1461.

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In cells of the teleost retinal pigment epithelium (RPE), melanin granules disperse into the RPE cell's long apical projections in response to light onset, and aggregate toward the base of the RPE cell in response to dark onset. The RPE cells possess numerous microtubules, which in the apical projections are aligned longitudinally. Nocodazole studies have shown that pigment granule aggregation is microtubule-dependent (Troutt, L. L., and B. Burnside, 1988b Exp. Eye Res. In press.). To investigate further the mechanism of microtubule participation in RPE pigment granule aggregation, we have use
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Yang, Jee Myung, Sunho Chung, KyungA Yun, et al. "Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats." Experimental & Molecular Medicine 53, no. 4 (2021): 631–42. http://dx.doi.org/10.1038/s12276-021-00588-w.

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AbstractRetinal degenerative disorders, including age-related macular degeneration and retinitis pigmentosa (RP), are characterized by the irreversible loss of photoreceptor cells and retinal pigment epithelial (RPE) cells; however, the long-term effect of implanting both human induced pluripotent stem cell (hiPSC)-derived RPE and photoreceptor for retinal regeneration has not yet been investigated. In this study, we evaluated the long-term effects of hiPSC-derived RPE and photoreceptor cell transplantation in Pde6b knockout rats to study RP; cells were injected into the subretinal space of th
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Percopo, C. M., J. J. Hooks, T. Shinohara, R. Caspi, and B. Detrick. "Cytokine-mediated activation of a neuronal retinal resident cell provokes antigen presentation." Journal of Immunology 145, no. 12 (1990): 4101–7. http://dx.doi.org/10.4049/jimmunol.145.12.4101.

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Abstract The retinal pigment epithelial (RPE) cell has long been considered an important regulatory cell, maintaining physiological and structural balance within the retina. We have previously shown that the RPE cell may also be important in autoimmunity and transplantation. These cells can be induced by cytokines to express MHC class II Ag in ocular inflammatory and autoimmune conditions. In this report we show that isolated rat RPE cells can be induced to express class II Ag following incubation with rat rIFN-gamma. The ability of RPE cells to present Ag was determined by both T cell prolife
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23

Esteve-Rudd, Julian, Roni A. Hazim, Tanja Diemer, et al. "Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration." Proceedings of the National Academy of Sciences 115, no. 21 (2018): 5468–73. http://dx.doi.org/10.1073/pnas.1709211115.

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Stargardt macular dystrophy 3 (STGD3) is caused by dominant mutations in the ELOVL4 gene. Like other macular degenerations, pathogenesis within the retinal pigment epithelium (RPE) appears to contribute to the loss of photoreceptors from the central retina. However, the RPE does not express ELOVL4, suggesting photoreceptor cell loss in STGD3 occurs through two cell nonautonomous events: mutant photoreceptors first affect RPE cell pathogenesis, and then, second, RPE dysfunction leads to photoreceptor cell death. Here, we have investigated how the RPE pathology occurs, using a STGD3 mouse model
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Zou, Hui, Chenli Shan, Linlin Ma, Jia Liu, Ning Yang, and Jinsong Zhao. "Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy." PeerJ 8 (October 20, 2020): e10136. http://dx.doi.org/10.7717/peerj.10136.

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Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells. Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions. In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachmen
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25

Rzhanova, Lyubov A., Yuliya V. Markitantova, and Maria A. Aleksandrova. "Recent Achievements in the Heterogeneity of Mammalian and Human Retinal Pigment Epithelium: In Search of a Stem Cell." Cells 13, no. 3 (2024): 281. http://dx.doi.org/10.3390/cells13030281.

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Retinal pigment epithelium (RPE) cells are important fundamentally for the development and function of the retina. In this regard, the study of the morphological and molecular properties of RPE cells, as well as their regenerative capabilities, is of particular importance for biomedicine. However, these studies are complicated by the fact that, despite the external morphological similarity of RPE cells, the RPE is a population of heterogeneous cells, the molecular genetic properties of which have begun to be revealed by sequencing methods only in recent years. This review carries out an analys
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Mora, Rosalia C., Vera L. Bonilha, Bo-Chul Shin, et al. "Bipolar assembly of caveolae in retinal pigment epithelium." American Journal of Physiology-Cell Physiology 290, no. 3 (2006): C832—C843. http://dx.doi.org/10.1152/ajpcell.00405.2005.

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Caveolae and their associated structural proteins, the caveolins, are specialized plasmalemmal microdomains involved in endocytosis and compartmentalization of cell signaling. We examined the expression and distribution of caveolae and caveolins in retinal pigment epithelium (RPE), which plays key roles in retinal support, visual cycle, and acts as the main barrier between blood and retina. Electron microscopic observation of rat RPE, in situ primary cultures of rat and human RPE and a rat RPE cell line (RPE-J) demonstrated in all cases the presence of caveolae in both apical and basolateral d
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Sharma, Ruchi, Vladimir Khristov, Aaron Rising, et al. "Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs." Science Translational Medicine 11, no. 475 (2019): eaat5580. http://dx.doi.org/10.1126/scitranslmed.aat5580.

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Considerable progress has been made in testing stem cell–derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-gra
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Si, Zhibo, Yajuan Zheng, and Jing Zhao. "The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy." Biomolecules 13, no. 6 (2023): 901. http://dx.doi.org/10.3390/biom13060901.

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Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell proliferation and choroidal angiogenesis. The retinal pigment epithelium (RPE) plays a key role in AMD pathogenesis. In particular, helioreceptor renewal depends on outer segment phagocytosis of RPE cells, while RPE autophagy can protect cells from oxidative stress damage. However, when the oxidative stress burden is too high and homeostasis is disturbed, the phagocytosis and autophagy functions of RPE become damaged, leading to A
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Rajendran Nair, Deepthi S., Danhong Zhu, Ruchi Sharma, et al. "Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats." Cells 10, no. 11 (2021): 2951. http://dx.doi.org/10.3390/cells10112951.

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Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In many preclinical studies, RPE cells are transplanted as a cell suspension into immunosuppressed animal eyes and transplant effects have been monitored only short-term. We investigated the long-term effects of human Induced pluripotent stem-cell-derived RPE (iPSC-RPE) transplants in an immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction led to photoreceptor degeneration. iPSC-RPE cultured as a polarized monolayer on a nanoeng
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Marmorstein, Alan D., Yunbo C. Gan, Vera L. Bonilha, Silvia C. Finnemann, Karl G. Csaky, and Enrique Rodriguez-Boulan. "Apical Polarity of N-CAM and EMMPRIN in Retinal Pigment Epithelium Resulting from Suppression of Basolateral Signal Recognition." Journal of Cell Biology 142, no. 3 (1998): 697–710. http://dx.doi.org/10.1083/jcb.142.3.697.

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Retinal pigment epithelial (RPE) cells apically polarize proteins that are basolateral in other epithelia. This reversal may be generated by the association of RPE with photoreceptors and the interphotoreceptor matrix, postnatal expansion of the RPE apical surface, and/or changes in RPE sorting machinery. We compared two proteins exhibiting reversed, apical polarities in RPE cells, neural cell adhesion molecule (N-CAM; 140-kD isoform) and extracellular matrix metalloproteinase inducer (EMMPRIN), with the cognate apical marker, p75-neurotrophin receptor (p75-NTR). N-CAM and p75-NTR were apicall
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31

Shang, Peng, Nadezda A. Stepicheva, Haitao Liu, et al. "A Novel Method of Mouse RPE Explant Culture and Effective Introduction of Transgenes Using Adenoviral Transduction for In Vitro Studies in AMD." International Journal of Molecular Sciences 22, no. 21 (2021): 11979. http://dx.doi.org/10.3390/ijms222111979.

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Degeneration of retinal pigment epithelium (RPE) is one of the most critical phenotypic changes of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. While cultured polarized RPE cells with original properties are valuable in in vitro models to study RPE biology and the consequences of genetic and/or pharmacological manipulations, the procedure to establish mouse primary PRE cell culture or pluripotent stem cell-derived RPE cells is time-consuming and yields a limited number of cells. Thus, establishing a mouse in situ RPE culture system is highly desirabl
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Park, Sun Young, Woo Chang Song, Beomjin Kim, Jin-Woo Oh, and Geuntae Park. "Nano-Graphene Oxide-Promoted Epithelial–Mesenchymal Transition of Human Retinal Pigment Epithelial Cells through Regulation of Phospholipase D Signaling." Nanomaterials 11, no. 10 (2021): 2546. http://dx.doi.org/10.3390/nano11102546.

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Nano-graphene oxide (Nano-GO) is an extensively studied multifunctional carbon nanomaterial with attractive applications in biomedicine and biotechnology. However, few studies have been conducted to assess the epithelial-to-mesenchymal transition (EMT) in the retinal pigment epithelium (RPE). We aimed to determine whether Nano-GO induces EMT by regulating phospholipase D (PLD) signaling in human RPE (ARPE-19) cells. The physicochemical characterization of Nano-GO was performed using a Zetasizer, X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy. R
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Zhang, Yibing, Min Li, and Xue Han. "Icariin affects cell cycle progression and proliferation of human retinal pigment epithelial cells via enhancing expression of H19." PeerJ 8 (March 20, 2020): e8830. http://dx.doi.org/10.7717/peerj.8830.

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Background Aberrant proliferation of retinal pigment epithelial (RPE) cells under pathologic condition results in the occurrence of proliferative vitreoretinopathy (PVR). Icariin (ICA)-a flavonol glucoside-has been shown to inhibit proliferation of many cell types, but the effect on RPE cells is unknown. This study aimed to clarify the inhibitory effects of ICA on RPE cells against platelet-derived growth factor (PDGF)-BB-induced cell proliferation, and discuss the regulatory function of H19 in RPE cells. Methods MTS assay was conducted to determine the effects of ICA on cell proliferation. Fl
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Mäenpää, Hanna, Tarja Toimela, Pirjo Saransaari, Lotta Salminen, and Hanna Tähti. "Mechanism of Tamoxifen's Retinal Toxicity, Studied in Pig Pigment Epithelial Cell Cultures." Alternatives to Laboratory Animals 25, no. 3 (1997): 297–302. http://dx.doi.org/10.1177/026119299702500310.

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The anticancer drug tamoxifen is widely used in breast cancer therapy. Tamoxifen has been reported to cause ocular toxicity and impairment of vision in epidemiological studies. To study the possible role of an excitotoxic mechanism in the ocular toxicity of tamoxifen, we investigated the effect of tamoxifen on retinal pigment epithelium (RPE) glutamate uptake in vitro. RPE, a layer of cells between photoreceptors and choroidal capillaries, contributes to the regulation of the concentration of the major excitatory amino acid, glutamate, in the sub-retinal space. Dysfunction in RPE glutamate upt
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35

Fanelli, Giorgia, Marco Romano, Giovanna Lombardi, and Steven H. Sacks. "Soluble Collectin 11 (CL-11) Acts as an Immunosuppressive Molecule Potentially Used by Stem Cell-Derived Retinal Epithelial Cells to Modulate T Cell Response." Cells 12, no. 13 (2023): 1805. http://dx.doi.org/10.3390/cells12131805.

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Retinal pigment epithelium (RPE) cell allotransplantation is seen as a possible solution to retinal diseases. However, the RPE-complement system triggered by the binding of collectin-11 (CL-11) is a potential barrier for RPE transplantation as the complement-mediated inflammatory response may promote T cell recognition. To address this, we investigated the role of CL-11 on T cell immuno-response. We confirmed that RPE cells up-regulated MHC class I and expressed MHC class II molecules in an inflammatory setting. Co-cultures of RPE cells with T cells led to the inhibition of T cell proliferatio
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36

Takayama, Kei, Hiroki Kaneko, Keiko Kataoka, et al. "Nuclear Factor (Erythroid-Derived)-Related Factor 2-Associated Retinal Pigment Epithelial Cell Protection under Blue Light-Induced Oxidative Stress." Oxidative Medicine and Cellular Longevity 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/8694641.

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Purpose. It is a matter of increasing concern that exposure to light-emitting diodes (LED), particularly blue light (BL), damages retinal cells. This study aimed to investigate the retinal pigment epithelium (RPE) damage caused by BL and to elucidate the role of nuclear factor (erythroid-derived)-related factor 2 (Nrf2) in the pathogenesis of BL-induced RPE damage.Methods. ARPE-19, a human RPE cell line, and mouse primary RPE cells from wild-type andNrf2knockout (Nrf2−/−) mice were cultured under blue LED exposure (intermediate wavelength, 450 nm). Cell death rate and reactive oxygen species (
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37

Abdouh, Mohamed, Yunxi Chen, Alicia Goyeneche, and Miguel N. Burnier. "Blue Light-Induced Mitochondrial Oxidative Damage Underlay Retinal Pigment Epithelial Cell Apoptosis." International Journal of Molecular Sciences 25, no. 23 (2024): 12619. http://dx.doi.org/10.3390/ijms252312619.

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Reactive oxygen species (ROS) play a pivotal role in apoptosis. We reported that Blue Light (BL) induced oxidative stress in human retinal pigment epithelial (RPE) cells in vitro and increased drusen deposition and RPE cell apoptosis in human eyes. Here, we investigated the mechanisms underlying BL-induced damage to RPE cells. Cells were exposed to BL with or without the antioxidant N-acetylcysteine. Cells were analyzed for levels of ROS, proliferation, viability, and mitochondria membrane potential (ΔΨM) fluctuation. We performed proteomic analyses to search for differentially expressed prote
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38

Zhu, Xin-Yue, Ting Zhang, Su-Jun Liu, et al. "Improvement of human embryonic stem cell-derived retinal pigment epithelium cell adhesion, maturation, and function through coating with truncated recombinant human vitronectin." International Journal of Ophthalmology 14, no. 8 (2021): 1160–67. http://dx.doi.org/10.18240/ijo.2021.08.04.

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AIM: To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial (hES-RPE) cells in vitro, and compare the behaviors and functions of hES-RPE cells on two culture substrates, laminin521 (LN-521) and truncated recombinant human vitronectin (VTN-N). METHODS: hES-RPE cells were used in the experiment. The abilities of LN-521 and VTN-N at different concentrations to adhere to hES-RPE cells were compared with a high-content imaging system. Quantitative real-time polymerase chain reaction was used to evaluate RPE-s
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Ishida, Masaaki, Sunao Sugita, Kenichi Makabe, et al. "A ROCK Inhibitor Promotes Graft Survival during Transplantation of iPS-Cell-Derived Retinal Cells." International Journal of Molecular Sciences 22, no. 6 (2021): 3237. http://dx.doi.org/10.3390/ijms22063237.

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Currently, retinal pigment epithelium (RPE) transplantation includes sheet and single-cell transplantation, the latter of which includes cell death and may be highly immunogenic, and there are some issues to be improved in single-cell transplantation. Y-27632 is an inhibitor of Rho-associated protein kinase (ROCK), the downstream kinase of Rho. We herein investigated the effect of Y-27632 in vitro on retinal pigment epithelium derived from induced pluripotent stem cells (iPS-RPE cells), and also its effects in vivo on the transplantation of iPS-RPE cell suspensions. As a result, the addition o
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Wei, Ying, Uwimana Alexandre, and Xiang Ma. "Hydrogels to Support Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells." Brain Sciences 12, no. 12 (2022): 1620. http://dx.doi.org/10.3390/brainsci12121620.

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Purpose: Retinal pigment epithelial (RPE) cells are highly specialized neural cells with several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and, ultimately, blinding disease. While human embryonic stem cell-derived RPE cell (hESC-RPE) growth conditions are generally harsher than those of cell lines, the subretinal transplantation of hESC-RPE is being clinically explored as a strategy to recover the damaged retina and improve vision. The cell-adhesion ability of the support is required for RPE transplantation, wh
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41

Chen, Shiu-Jau, Tzer-Bin Lin, Hsien-Yu Peng, et al. "Cytoprotective Potential of Fucoxanthin in Oxidative Stress-Induced Age-Related Macular Degeneration and Retinal Pigment Epithelial Cell Senescence In Vivo and In Vitro." Marine Drugs 19, no. 2 (2021): 114. http://dx.doi.org/10.3390/md19020114.

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Oxidative stress is identified as a major inducer of retinal pigment epithelium (RPE) cell dysregulation and is associated with age-related macular degeneration (AMD). The protection of RPE disorders plays an essential role in the pathological progress of retinal degeneration diseases. The pharmacological functions of fucoxanthin, a characteristic carotenoid, including anti-inflammatory and antioxidant properties, may ameliorate an outstanding bioactivity against premature senescence and cellular dysfunction. This study demonstrates that fucoxanthin protects RPE cells from oxidative stress-ind
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42

Maruotti, Julien, Srinivas R. Sripathi, Kapil Bharti, et al. "Small-molecule–directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells." Proceedings of the National Academy of Sciences 112, no. 35 (2015): 10950–55. http://dx.doi.org/10.1073/pnas.1422818112.

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Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule–only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented
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O’Neill, Helen C., Ioannis J. Limnios, and Nigel L. Barnett. "Advancing a Stem Cell Therapy for Age-Related Macular Degeneration." Current Stem Cell Research & Therapy 15, no. 2 (2020): 89–97. http://dx.doi.org/10.2174/1574888x15666191218094020.

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The retinal pigment epithelium (RPE) is a multifunctional monolayer located at the back of the eye required for the survival and function of the light-sensing photoreceptors. In Age-related Macular Degeneration (AMD), the loss of RPE cells leads to photoreceptor death and permanent blindness. RPE cell transplantation aims to halt or reverse vision loss by preventing the death of photoreceptor cells and is considered one of the most viable applications of stem cell therapy in the field of regenerative medicine. Proof-of-concept of RPE cell transplantation for treating retinal degenerative disea
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Kiamehr, Mostafa, Alexa Klettner, Elisabeth Richert, et al. "Compromised Barrier Function in Human Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells from Type 2 Diabetic Patients." International Journal of Molecular Sciences 20, no. 15 (2019): 3773. http://dx.doi.org/10.3390/ijms20153773.

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In diabetic patients, high blood glucose induces alterations in retinal function and can lead to visual impairment due to diabetic retinopathy. In immortalized retinal pigment epithelial (RPE) cultures, high glucose concentrations are shown to lead to impairment in epithelial barrier properties. For the first time, the induced pluripotent stem-cell-derived retinal pigment epithelium (hiPSC-RPE) cell lines derived from type 2 diabetics and healthy control patients were utilized to assess the effects of glucose concentration on the cellular functionality. We show that both type 2 diabetic and he
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Hellinen, Pirskanen, Tengvall-Unadike, Urtti, and Reinisalo. "Retinal Pigment Epithelial Cell Line with Fast Differentiation and Improved Barrier Properties." Pharmaceutics 11, no. 8 (2019): 412. http://dx.doi.org/10.3390/pharmaceutics11080412.

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Retinal pigment epithelium (RPE) acts as an outer blood–retinal barrier that limits the access of circulating xenobiotics to the eye. In addition, the RPE limits posterior elimination of intravitreally injected drugs to circulation. Thus, permeation in the RPE has a significant effect on ocular pharmacokinetics. The RPE is also a potentially important drug target in age-related macular degeneration. Therefore, the cell models of the RPE are important tools in ocular drug development, but poor availability and problems in reproducibility limit the use of primary RPE cell cultures. Furthermore,
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Lou, Hui, Chunpin Lian, Fanjun Shi, et al. "The Petri Dish-N2B27 Culture Condition Maintains RPE Phenotype by Inhibiting Cell Proliferation and mTOR Activation." Journal of Ophthalmology 2020 (August 14, 2020): 1–12. http://dx.doi.org/10.1155/2020/4892978.

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Objective. To develop a method for the rapid isolation of rat RPE cells with high yield and maintain its epithelial state in modified culture system. Methods. The eyeballs were incubated with dispase. The retina was isolated with RPE attached and cut into several pieces. Following a brief incubation in growth medium, large RPE sheets can be harvested rapidly. RPE cells were divided into four groups and cultured for several weeks, that is, (1) in cell culture dishes with 10% FBS containing medium (CC dish-FBS), (2) in petri dishes with 10% FBS containing medium (Petri dish-FBS), (3) in cell cul
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47

Nabi, I. R., A. P. Mathews, L. Cohen-Gould, D. Gundersen, and E. Rodriguez-Boulan. "Immortalization of polarized rat retinal pigment epithelium." Journal of Cell Science 104, no. 1 (1993): 37–49. http://dx.doi.org/10.1242/jcs.104.1.37.

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Rat retinal pigment epithelial (RPE) cells were immortalized by infection with a temperature-sensitive tsA SV40 virus and following cloning and selection for epithelial properties the polarized RPE-J cell line was obtained. At the permissive temperature of 33 degrees C, RPE-J cells behave as an immortalized cell line. When RPE-J cells are grown on nitrocellulose filters coated with a thin layer of Matrigel in the presence of 10(−8) M retinoic acid for 6 days at 33 degrees C and then switched for 33–36 hours to the non-permissive temperature of 40 degrees C, they acquire a differentiated polari
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Ng, Eunice Sze Yin, Nermin Kady, Jane Hu, et al. "Membrane Attack Complex Mediates Retinal Pigment Epithelium Cell Death in Stargardt Macular Degeneration." Cells 11, no. 21 (2022): 3462. http://dx.doi.org/10.3390/cells11213462.

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Recessive Stargardt disease (STGD1) is an inherited retinopathy caused by mutations in the ABCA4 gene. The ABCA4 protein is a phospholipid-retinoid flippase in the outer segments of photoreceptors and the internal membranes of retinal pigment epithelial (RPE) cells. Here, we show that RPE cells derived via induced pluripotent stem-cell from a molecularly and clinically diagnosed STGD1 patient exhibited reduced ABCA4 protein and diminished activity compared to a normal subject. Consequently, STGD1 RPE cells accumulated intracellular autofluorescence-lipofuscin and displayed increased complement
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Schustak, Joshua, Hongwei Han, Kyle Bond, Qian Huang, Magali Saint-Geniez, and Yi Bao. "Phenotypic high-throughput screening identifies aryl hydrocarbon receptor agonism as common inhibitor of toxin-induced retinal pigment epithelium cell death." PLOS ONE 19, no. 4 (2024): e0301239. http://dx.doi.org/10.1371/journal.pone.0301239.

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The retinal pigment epithelium (RPE) is essential to maintain retinal function, and RPE cell death represents a key pathogenic stage in the progression of several blinding ocular diseases, including age-related macular degeneration (AMD). To identify pathways and compounds able to prevent RPE cell death, we developed a phenotypic screening pipeline utilizing a compound library and high-throughput screening compatible assays on the human RPE cell line, ARPE-19, in response to different disease relevant cytotoxic stimuli. We show that the metabolic by-product of the visual cycle all-trans-retina
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Gnana-Prakasam, Jaya P., Muthusamy Thangaraju, Kebin Liu, et al. "Absence of iron-regulatory protein Hfe results in hyperproliferation of retinal pigment epithelium: role of cystine/glutamate exchanger." Biochemical Journal 424, no. 2 (2009): 243–52. http://dx.doi.org/10.1042/bj20090424.

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Haemochromatosis is an iron-overload disorder with age-dependent oxidative stress and dysfunction in a variety of tissues. Mutations in HFE (histocompatability leucocyte antigen class I-like protein involved in iron homoeostasis) are responsible for most cases of haemochromatosis. We demonstrated recently that HFE is expressed exclusively in the basal membrane of RPE (retinal pigment epithelium). In the present study, we used Hfe−/− mice to examine ferritin levels (an indirect readout for iron levels) and morphological changes in retina. We found increased ferritin accumulation in retina in 18
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