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Dissertations / Theses on the topic 'Retinal Cone Photoreceptor Cells'
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1
Bumsted, Keely Maureen. "The role of opsin expression in the development of photoreceptor topography and synapses in the fetal primate retina /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/5679.
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Dunn, Felice Audris. "Gain control of rod and cone vision in the mammalian retina /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10642.
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Kennedy, Matthew James. "Turning off the light response in rod and cone photoreceptors /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/9217.
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Rubin, Glen R. "Comparisons between behavioral and electrophysiological measures of visual function in rodent models of retinal degeneration." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2009p/rubin.pdf.
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McDougal, David H. "The role of melanopsin containing retinal ganglion cells in the pupillary responses of human and non-human primates." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/mcdougal.pdf.
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Venkatesh, Aditya. "Activation of mTORC1 Improves Cone Cell Metabolism and Extends Vision in Retinitis Pigmentosa Mice: A Dissertation." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/822.
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Retinitis Pigmentosa (RP) is an inherited photoreceptor degenerative disease that leads to blindness and affects about 1 in 4000 people worldwide. The disease is predominantly caused by mutations in genes expressed exclusively in the night active rod photoreceptors; however, blindness results from the secondary loss of the day active cone photoreceptors, the mechanism of which remains elusive. Here, we show that the mammalian target of rapamycin complex 1 (mTORC1) is required to delay the progression of cone death during disease and that constitutive activation of mTORC1 is sufficient to maintain cone function and promote cone survival in RP. Activation of mTORC1 increased expression of genes that promote glucose uptake, retention and utilization, leading to increased NADPH levels; a key metabolite for cones. This protective effect was conserved in two mouse models of RP, indicating that the secondary loss of cones can be delayed by an approach that is independent of the primary mutation in rods. However, since mTORC1 is a negative regulator of autophagy, its constitutive activation led to an unwarranted secondary effect of shortage of amino acids due to incomplete digestion of autophagic cargo, which reduces the efficiency of cone survival over time. Moderate activation of mTORC1, which promotes expression of glycolytic genes, as well as maintains autophagy, provided more sustained cone survival. Together, our work addresses a long-standing question of non-autonomous cone death in RP and presents a novel, mutation-independent approach to extend vision in a disease that remains incurable.
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Venkatesh, Aditya. "Activation of mTORC1 Improves Cone Cell Metabolism and Extends Vision in Retinitis Pigmentosa Mice: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/822.
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Retinitis Pigmentosa (RP) is an inherited photoreceptor degenerative disease that leads to blindness and affects about 1 in 4000 people worldwide. The disease is predominantly caused by mutations in genes expressed exclusively in the night active rod photoreceptors; however, blindness results from the secondary loss of the day active cone photoreceptors, the mechanism of which remains elusive. Here, we show that the mammalian target of rapamycin complex 1 (mTORC1) is required to delay the progression of cone death during disease and that constitutive activation of mTORC1 is sufficient to maintain cone function and promote cone survival in RP. Activation of mTORC1 increased expression of genes that promote glucose uptake, retention and utilization, leading to increased NADPH levels; a key metabolite for cones. This protective effect was conserved in two mouse models of RP, indicating that the secondary loss of cones can be delayed by an approach that is independent of the primary mutation in rods. However, since mTORC1 is a negative regulator of autophagy, its constitutive activation led to an unwarranted secondary effect of shortage of amino acids due to incomplete digestion of autophagic cargo, which reduces the efficiency of cone survival over time. Moderate activation of mTORC1, which promotes expression of glycolytic genes, as well as maintains autophagy, provided more sustained cone survival. Together, our work addresses a long-standing question of non-autonomous cone death in RP and presents a novel, mutation-independent approach to extend vision in a disease that remains incurable.
8
Huang, Daming. "Molecular determinants of cGMP-binding to chicken cone photoreceptor phosphodiesterase /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/5095.
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Mencl, Stine [Verfasser], and Eberhart [Akademischer Betreuer] Zrenner. "Mechanisms of cone photoreceptor cell death in models for inherited retinal degeneration / Stine Mencl ; Betreuer: Eberhart Zrenner." Tübingen : Universitätsbibliothek Tübingen, 2013. http://d-nb.info/1162843748/34.
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Aslam, Sher A. "Investigating treatment options for battlefield retinal laser injury." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:0f3677ac-90d2-4e38-86cd-9d514d3d9755.
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Battlefield retinal laser injury is an infrequent but potentially devastating cause of irreversible blindness. Resultant laser-induced photoreceptor death may occur by necrosis or apoptosis, the latter which is a form of programmed cell death that may be physiological or pathological. Though necrosis cannot be prevented, apoptosis may be inhibited under certain conditions. Therefore, following retinal laser injury, specific treatment aims to target apoptotic photoreceptors and may take the form of neuroprotection or cell replacement. The primary aim of this thesis was to construct an in vivo model in which to observe the effects of retinal laser exposure on cone photoreceptor apoptosis. Current methodology to determine the effects involves histological techniques and is therefore limited to being cross-sectional. An in vivo model would permit longitudinal study to observe the cone response to injury using clinically relevant applications, including fundus autofluorescence imaging. Such a construct would enable more sensitive evaluation of new therapies which would be of direct translational relevance. The secondary aim was to investigate potential therapeutic options for retinal laser injury by pharmacological means in the form of CNTF or cell transplantation. To identify the possible molecular signals involved in neurotrophic factor-induced photoreceptor cell survival, apoptotic gene expression was investigated focusing on those genes modulated by the CNTF pathway.
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Markwell, Emma Louise. "Intrinsically photosensitive melanopsin retinal ganglion cell contributions to the post-illumination pupil response and circadian rhythm." Thesis, Queensland University of Technology, 2011. https://eprints.qut.edu.au/44136/1/Emma_Markwell_Thesis.pdf.
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Intrinsically photosensitive retinal ganglion cells (ipRGCs) in the eye transmit the environmental light level, projecting to the suprachiasmatic nucleus (SCN) (Berson, Dunn & Takao, 2002; Hattar, Liao, Takao, Berson & Yau, 2002), the location of the circadian biological clock, and the olivary pretectal nucleus (OPN) of the pretectum, the start of the pupil reflex pathway (Hattar, Liao, Takao, Berson & Yau, 2002; Dacey, Liao, Peterson, Robinson, Smith, Pokorny, Yau & Gamlin, 2005). The SCN synchronizes the circadian rhythm, a cycle of biological processes coordinated to the solar day, and drives the sleep/wake cycle by controlling the release of melatonin from the pineal gland (Claustrat, Brun & Chazot, 2005). Encoded photic input from ipRGCs to the OPN also contributes to the pupil light reflex (PLR), the constriction and recovery of the pupil in response to light. IpRGCs control the post-illumination component of the PLR, the partial pupil constriction maintained for > 30 sec after a stimulus offset (Gamlin, McDougal, Pokorny, Smith, Yau & Dacey, 2007; Kankipati, Girkin & Gamlin, 2010; Markwell, Feigl & Zele, 2010). It is unknown if intrinsic ipRGC and cone-mediated inputs to ipRGCs show circadian variation in their photon-counting activity under constant illumination. If ipRGCs demonstrate circadian variation of the pupil response under constant illumination in vivo, when in vitro ipRGC activity does not (Weng, Wong & Berson, 2009), this would support central control of the ipRGC circadian activity. A preliminary experiment was conducted to determine the spectral sensitivity of the ipRGC post-illumination pupil response under the experimental conditions, confirming the successful isolation of the ipRGC response (Gamlin, et al., 2007) for the circadian experiment. In this main experiment, we demonstrate that ipRGC photon-counting activity has a circadian rhythm under constant experimental conditions, while direct rod and cone contributions to the PLR do not. Intrinsic ipRGC contributions to the post-illumination pupil response decreased 2:46 h prior to melatonin onset for our group model, with the peak ipRGC attenuation occurring 1:25 h after melatonin onset. Our results suggest a centrally controlled evening decrease in ipRGC activity, independent of environmental light, which is temporally synchronized (demonstrates a temporal phase-advanced relationship) to the SCN mediated release of melatonin. In the future the ipRGC post-illumination pupil response could be developed as a fast, non-invasive measure of circadian rhythm. This study establishes a basis for future investigation of cortical feedback mechanisms that modulate ipRGC activity.
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Taylor, Michael Robert. "Genetic and biochemical analysis of zebrafish with visual function defects /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/9242.
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Baron, M. "Towards cone photoreceptor transplantation for retinal repair." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1344178/.
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Photoreceptors, the light sensing neurons of the retina, are pivotal to human vision. Degenerative diseases of the retina leading to photoreceptor death are a prime cause of untreatable blindness. In particular, loss of cone photoreceptors, which convey high visual acuity and colour perception, most severely affects central vision. This thesis investigates the possibility of replacement of lost cone photoreceptors by transplantation. The cone-rod homoeobox gene (Crx) is expressed in developing cone and rod photoreceptors cells. This thesis examines the potential of Crxexpressing cells to generate new cone and rod photoreceptors after transplantation into adult retinae. The expression of a novel photoreceptorspecic CrxGFP transgenic reporter mouse was characterised. In order to confirm the nuclear retinoid x receptor gamma (Rxrγ) as an early cone marker, BrdU pulse chase time-course experiments were performed utilising the reporter line as a marker for post-mitotic photoreceptors. To assess the efficacy of CrxGFP photoreceptor precursors for therapy and determine a suitable ontogenetic stage for cone transplantation, precursor cells were isolated from embryonic and early postnatal retinae by FACS and transplanted into adult retinae. Cells integrated and developed into mature cone and rod photoreceptors, distinguished by morphology and Rxrγ staining. Cone photoreceptors were only detected when embryonic donor cells were used, while rods integrated at all time-points, although integration efficiency was highest with post-natal donors. Integrated photoreceptors stained for a variety of functional rod and cone proteins, as well as several synaptic markers. In order to expose precursor cells to different recipient environments, embryonic precursors were also transplanted into two models of retinal degeneration. While the outer limiting membrane defects of the Crb1rd8/rd8 mouse had no significant impact on photoreceptor integration, the lack of cones in the Gucy2e-/- model led to significantly increased cone integration. Attempts were also made to derive an equivalent transplantable photoreceptor precursor cell species from renewable stem cell sources. Ciliary epithelium-derived cells, which can be isolated from the adult eye and were previously attributed with retinal stem cell qualities, were expanded in culture, but no evidence for photoreceptor differentiation was found. Embryonic stem cells were differentiated towards a retinal lineage and an RxrγRFP transgene reporter was introduced in order to label ES cell derived cone photoreceptors. These studies show for the first time that new cone cells can integrate into the adult retina and contribute to the development of stem cell therapy for retinal degenerative disease.
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Lee, E. J. K. "Cone photoreceptor neuroprotection in inherited retinal degenerations." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1346462/.
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High resolution and colour vision is derived from cone photoreceptors within the retina of the eye. These highly specialised neuronal cells convert energy from incident light into changes in cellular membrane potential. Action potentials are then relayed and processed within the inner retina and the cerebral cortex. Loss of function in the cone photoreceptors is the direct cause of visual loss for millions o f patients. Yet for many of the most common causes of blindness cone photoreceptor dysfunction occurs late on in the disease and is secondary to inherited and/or environmental influences that primarily affect other cell types. Cone photoreceptors are then secondarily affected and it is once their function is lost that the patient becomes visually disabled. The aim of this thesis was to evaluate therapies targeting the molecular steps of cone photoreceptor death rather than the underlying pathology. If effective at slowing cone photoreceptor degeneration and preserving function, such therapies could be applicable to large numbers of patients with a variety of underlying defects. There will however be continued stimuli for cell death as the primary defect has not been corrected and so it is important to determine the magnitude and duration of any treatment effect. The experiments of this thesis were performed in an animal model of inherited retinal degeneration derived to allow repeated in vivo assessments of cone photoreceptor function and survival. Gene therapy and intra-ocular injections were used to evaluate proteins with contrasting modes of action.
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Zabala, Aldunate E. "Role of microRNAs in cone photoreceptor development and during retinal degeneration." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1571896/.
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Photoreceptors are the light sensitive neurons in the retina that are critical for vision. Retinal dystrophies leading to photoreceptor cell loss are a major cause of blindness and there are currently no effective treatments to restore vision. Specifically, cone photoreceptor cell death has the greatest impact on sight as these cells are essential for colour vision and visual acuity. microRNAs (miRNAs) have been associated with the aetiology of common retinal diseases and whilst increasing evidence indicates they could be acting as agents of degeneration, their role in photoreceptor cell death remains poorly understood. This thesis aims to better understand how miRNAs are involved in the mechanisms leading to cone photoreceptor cell loss. The Chrnb4-GFP reporter mouse line was characterised and its expression in developing immature cones was confirmed by immunohistochemistry and validated by RNA sequencing. Successful isolation and RNA sequencing of Chrnb4-GFP+ve cones and CD73+ve rods was achieved from the same pool of retinas, allowing for a direct comparison of the transcriptome of cones and rods, and thus identifying potential novel cone markers. To assess the role of miRNAs in cone degeneration, Chrnb4-cre driven recombination of Dicer was carried out in developing cone photoreceptors. Chrnb4-cre; Dicer flox/flox conditional knockout mice displayed an early-onset progressive cone photoreceptor degeneration, characterised by an initial segment impairment and a progressive cone cell loss. While cone morphology and survival was affected by Dicer depletion, rod photoreceptors remained unaffected. These data indicate that miRNA dysregulation can lead to a model of cone dystrophy and suggests miRNAs may be major contributors in photoreceptor degenerations. This study shows for the first time that Dicer processing in developing cones is essential for their survival, and emphasises the need of identifying the specific miRNAs that promote cone survival with the goal of developing miRNA based therapies to tackle sight loss.
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Welby, Emily. "Isolating and characterising human developing cone photoreceptors towards a cell replacement therapy for retinal dystrophies." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1570501/.
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Inherited retinal dystrophies resulting in the death of the light sensitive photoreceptor cells are a major cause of incurable blindness. Loss of the cone photoreceptor cells, which are crucial for colour detection, daylight vision and high visual acuity, has the greatest impact on sight. Retinal differentiation of human pluripotent stem cells (hPSCs) provides a potential renewable source of cone photoreceptors for cell replacement therapy. However many critical challenges remain to be addressed, including i) assessing the similarity between the transcriptomes of bona fide human foetal and in vitro hPSC-derived cone cells and ii) developing strategies to purify cones prior to transplantation. The work in this thesis addresses these questions in relation to L/M-opsin photoreceptors, which form 90% of the total cone population in the human retina. The onset of cone photoreceptor markers in the developing human retina was characterised, before using an adeno-associated virus (AAV2/9.pR2.1:GFP) reporter to specifically label and isolate a foetal L/M-opsin cone population. Total mRNA sequencing revealed the transcriptome of this human foetal cone population for the first time and by performing differential gene expression analysis at early and late foetal timepoints, a novel cone-enriched gene signature was defined. Additionally, single cell transcriptome analysis revealed a subtle heterogeneity of these cone cells, which deviate based on maturity. Putative cell surface marker genes and cluster of differentiation (CD) marker proteins expressed by L/M-opsin cones were profiled, which led to a CD marker combination allowing for the enrichment of foetal L/M-opsin cones compared to the unsorted cell population via fluorescence activated cell sorting. Translating these tools into an hPSC-derived 3D retinal differentiation culture system revealed similarities in cone gene expression and cone cell enrichment post sorting to human foetal cone cells. Overall, these data provides vital pre-clinical steps towards generating a cone cell replacement therapy for retinal dystrophies.
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Chao, Christopher Chi Ying. "Modelling retinal photoreceptor directionality in the human eye." Thesis, Queensland University of Technology, 2002. https://eprints.qut.edu.au/36173/1/36173_Chao_2002.pdf.
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Retinal photoreceptor directionality of human eye refers to the fact that, for a normal and healthy human eye, visual sensitivity is greatest for light entering near the centre of the eye pupil and the response falls off from this peak roughly symmetrically across the pupil. This is also known as the Stiles-Crawford effect (SCE). It is achieved by the directionality of retinal cones that act like waveguides. It has a positive effect on
human vision since the optical aberrations of the eye normally increase in the pupil periphery. The measured SCE is used in clinical cases to indicate the stage and degree
of various retinal abnormalities. Directionality of human cones is traditionally measured either by psychophysical or reflectometric methods; several other methods
have also been proposed for measuring and modelling the cone directionality. Cone directionality and aberrations of the eye are widely varied from subject to subject. It
has been suggested that they are actively controlled and there may also exist a natural relationship between the directionality and aberrations. But the current methods to accurately measure the cone directionality are difficult and time consuming. In this research, we developed a mathematical model of the cone directionality based on the measured monochromatic aberrations of the human eye. We show that cone directionality can be modelled using a two-dimensional Gaussian function whose parameters vary according to the measured monochromatic aberrations of the eye. Our modelling is based on a hypothesis that cones directionality is optimised so that the
resulting retinal image quality is maximised. This methodology can also be used in
automatic image enhancement systems for correcting higher-order aberrations. The modelling of the SCE of the human eye as a Gaussian function has been demonstrated.
The optimisation process that we developed has been used to optimise ten different eyes, which all have significant amount of higher order aberrations. It has shown significant improvement in the corresponding Point Spread Functions. The proposed methodology could be used for cost-effective image enhancement in optical systems,
which suffer from higher-order monochromatic aberrations. Currently such systems have to be corrected with adaptive optics.
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Ivanovic, Ivana. "Biological significance of phosphoinositide-3 kinase in vertebrate retinal photoreceptor cells." Oklahoma City : [s.n.], 2009.
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Pant, Mukund. "Light adaptation of melanopsin photoreception and its interaction with cone signalling." Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/227063/1/Mukund%20Pant%20Thesis.pdf.
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Light adaptation optimises visual responses to illumination changes. Although it is well established that adaptation is faster for cone than rod photopigments, these dynamics are unknown for melanopsin photopigments in human eyes. This thesis reports the development of a novel method for characterising the melanopsin photobleach regeneration characteristic and its effect on the cone-driven pupil light reflex. Compared to cone-opsins, the melanopsin photopigment undergoes less bleaching in broadband light (~43% less) and with a slower regeneration rate (3.4X). During light adaptation, higher melanopsin excitations enhance the cone-mediated pupil response to improve visual contrast sensitivity.
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Robinson, Martha Rose. "Spatial and temporal dynamics of retinal ganglion cells with different photoreceptor inputs." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1572515/.
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The retina must operate over a wide range of light levels. Two classes of input cells, rods and cones, specialised to different light conditions evolved to achieve this task. This thesis examines how interactions between these two classes shape retinal output as the light level changes, and the extent to which loss of one class can alter processing of the remaining class. Retinal ganglion cell (RGC) receptive elds were characterised using multielectrode array recordings performed during presentation of spatiotemporal white noise across a 4.5 log10 light level range. Receptive fi eld properties were compared between wild-type mice, mice lacking functional cones (cpfl1 model of achromatopsia), and mice lacking functional rods (rd17 model of congenital stationary night blindness). The response of RGCs to otherwise identical stimuli changed with ambient light level. In low light conditions, wild-type RGCs had a longer latency to spike and were shifted towards higher temporal and lower spatial frequency tuning. Of those RGCs characterised at multiple light levels, 28% changed the polarity of their receptive fields between ON and OFF. These polarity switches occurred between every possible pair of light levels, and several cells were observed to switch multiple times. RGCs which switched polarity were identi ed in both rd17 and cpfl1 mice, indicating that at least some circuit mechanisms responsible are driven by a single photoreceptor cell class. Loss of function in one photoreceptor cell class altered visual processing of inputs from the remaining class. In low light conditions, RGCs in cpfl1 mice showed shorter latency to spike and a marked shift towards higher temporal frequency tuning, a receptive field property that is often understood as indicating tuning to visual motion. This difference in visual processing could result in behavioural differences, for instance these mice may exhibit better contrast sensitivity at temporal frequencies in low light conditions.
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Oishi, Akio. "Granulocyte colony stimulating factor protects retinal photoreceptor cells against light-induced damage." Kyoto University, 2009. http://hdl.handle.net/2433/124314.
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Locke, Christina. "In vivo cone photoreceptor imaging in adolescents as a measure of retinal stretch during refractive error development." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1554723728663165.
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Dey, Ashim. "Melanopsin photoreceptor contributions to brightness perception and photophobia." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/205723/1/Ashim_Dey_Thesis.pdf.
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This thesis investigated the role of rod, cone and melanopsin photoreceptors in mediating human brightness perception across the natural operating range of the eye. In scotopic illumination, brightness perception is initiated by rod signals transmitted to higher brain centres via conventional retinogeniculate and melanopsin pathways. In mesopic illumination, melanopsin photoreception begins to scale brightness perception. In photopic illumination, melanopsin and cone luminance signals combine to mediate light hypersensitivity (photophobia) in healthy controls and migraineurs. These findings advance understanding of the relative photoreceptor contributions to human vision and guide the development of lighting technologies for individuals who experience disease-related photophobia.
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Zaidi, Farhan Husain. "Novel photoreceptor cells, pupillometry and electrodiagnosis in orbital, vitreo-retinal and refractive disorders." Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/11962.
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Han, Y. "Towards retinal repair : analysis of photoreceptor precursor cells and their cell surface molecules." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1417170/.
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Photoreceptor cells are the sensory cells of the retina, responsible for detecting light and conducting the signals to secondary neurons. Because they cannot be regenerated, loss of photoreceptor cells leads to irreversible blindness. Cell transplantation with postmitotic photoreceptor precursor cells has been shown as a feasible approach to rescue vision in animal models, but the molecular properties of these transplantation-competent cells are not understood. The aims of this thesis are to 1) determine the properties of photoreceptor precursor cells by transcriptome and proteome analysis; 2) identify cell surface molecules that can be used to isolate these cells from cell mixtures and/or that are important for their migration and correct integration in development and in a transplantation context. Nrl/CrxGFP transgene-labelled photoreceptor precursor cells were separated from other retinal cells by flow cytometry and subjected to microarray and mass spectrometry analysis. Bioinformatics analysis showed that the photoreceptor precursor cells were enriched in expression of genes encoding cell projection proteins. Over 200 cell surface molecule candidates were identified and 32 genes encoding confirmed extracellular domains were expressed > 5-fold higher in photoreceptor precursors than other retinal cells. These included the stem cell marker Prom1 (CD133), which was specifically expressed in photoreceptor cells (particularly on their cilia) throughout development as well as on transplanted photoreceptors. Together with CD73 and CD24, it serves as a specific marker to isolate photoreceptor cells for transplantation. An axon guidance molecule Sema7a was shown to be highly expressed in photoreceptor cells. It co-labels with PlxnC1, rather than the expected receptor Itgb1, in developing retina, as well as transplanted migrating photoreceptor cells. Knockout of Sema7a resulted in retinal holes and abnormal photoreceptor synapse projection indicating a role of Sema7a in outer retina lamination. This study sets the foundation for future work on photoreceptor cell surface molecules in development and retinal repair.
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Lazareva, A. "An automated image processing system for the detection of photoreceptor cells in adaptive optics retinal images." Thesis, City, University of London, 2017. http://openaccess.city.ac.uk/19164/.
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The rapid progress in Adaptive Optics (AO) imaging, in the last decades, has had a transformative impact on the entire approach underpinning the investigations of retinal tissues. Capable of imaging the retina in vivo at the cellular level, AO systems have revealed new insights into retinal structures, function, and the origins of various retinal pathologies. This has expanded the field of clinical research and opened a wide range of applications for AO imaging. The advances in image processing techniques contribute to a better observation of retinal microstructures and therefore more accurate detection of pathological conditions. The development of automated tools for processing images obtained with AO allows for objective examination of a larger number of images with time and cost savings and thus facilitates the use of AO imaging as a practical and efficient tool, by making it widely accessible to the clinical ophthalmic community. In this work, an image processing framework is developed that allows for enhancement of AO high-resolution retinal images and accurate detection of photoreceptor cells. The proposed framework consists of several stages: image quality assessment, illumination compensation, noise suppression, image registration, image restoration, enhancement and detection of photoreceptor cells. The visibility of retinal features is improved by tackling specific components of the AO imaging system, affecting the quality of acquired retinal data. Therefore, we attempt to fully recover AO retinal images, free from any induced degradation effects. A comparative study of different methods and evaluation of their efficiency on retinal datasets is performed by assessing image quality. In order to verify the achieved results, the cone packing density distribution was calculated and correlated with statistical histological data. From the performed experiments, it can be concluded that the proposed image processing framework can effectively improve photoreceptor cell image quality and thus can serve as a platform for further investigation of retinal tissues. Quantitative analysis of the retinal images obtained with the proposed image processing framework can be used for comparison with data related to pathological retinas, as well as for understanding the effect of age and retinal pathology on cone packing density and other microstructures.
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Tucker, Chandra Lenore. "Structural and functional studies of retinal guanylyl cyclase /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/9272.
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Crespo, Catia [Verfasser], Elisabeth [Akademischer Betreuer] Knust, Elisabeth [Gutachter] Knust, and Marius [Gutachter] Ader. "Maturation of Photoreceptor Cells During Zebrafish Retinal Development / Catia Crespo ; Gutachter: Elisabeth Knust, Marius Ader ; Betreuer: Elisabeth Knust." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2018. http://d-nb.info/1226813119/34.
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Crespo, Catia Verfasser], Elisabeth [Akademischer Betreuer] [Knust, Elisabeth [Gutachter] Knust, and Marius [Gutachter] Ader. "Maturation of Photoreceptor Cells During Zebrafish Retinal Development / Catia Crespo ; Gutachter: Elisabeth Knust, Marius Ader ; Betreuer: Elisabeth Knust." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2018. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-237586.
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Kinkl, Norbert. "Mechanisms of action of fibroblast growth factor 2 (FGF2) in rat retinal cells : photoreceptor survival and intracellular signaling." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13166.
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La dégénérescence des photorécepteurs est à l'origine de nombreuses pathologies rétiniennes aboutissant à une malvoyance voire à la cécité. Les facteurs neurotrophiques représentent une approche thérapeutique potentielle. Au cours de cette thèse nous nous sommes intéressés aux mécanismes d'actions in vitro d'un facteur neurotrophique exprimé dans la rétine, le FGF2. Afin d'étudier les effets directs du FGF2 sur la survie des photorécepteurs, nous avons mis au point un nouveau modèle de culture pure en photorécepteurs à partir de rétine jeune de rat. La pureté en photorécepteurs des cultures est > 99,5%, les cellules gliales de Müller (CGM) représentant < 0,5% de la population cellulaire. Grâce à ce modèle, nous avons montré que le FGF2 stimule la survie des photorécepteurs in vitro et qu'un autre facteur neurotrophique, l'EGF, accélère leur dégénérescence, en activant leurs récepteurs respectifs à activité tyrosine kinase. Les FGFR1-4 ainsi que différentes protéines impliquées dans la transduction du signal du FGF2 (ERK1/2, MEK1, MEK2, PLCg1, SHPTP-2, SOS1, SOS2, Grb2, Shc, Akt), sont exprimés de façon ubiquitaire, mais possèdent des niveau d'expression distinct, selon les différentes populations de cellules rétiniennes (photorécepteurs, rétine interne et CGM) in vivo et in vitro. Néanmoins, le FGF2 y induit des cascades de signalisation distinctes. Ceci indique l'existence de différentes voies de transduction du signal au FGF2 dans la rétine aboutissant toutes à l'activation de ERK1/2. L'inhibition pharmacologique de MEK bloque l'activation de ERK1/2 dans les photorécepteurs et inhibe leur survie induit par le FGF2, alors qu'au niveau des cellules de la rétine interne et des CGM, le FGF2 stimule également des voies d'activation de ERK1/2 indépendantes de MEK. L'ensemble de ces résultats apporte des données originales concernant les effets du FGF2 sur la survie des photorécepteurs ainsi que sur sa signalisation dans la rétine de rat in vitro, et pourrait contribuer à une application potentielle du FGF2 dans une approche clinique.
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Kemmler, Robin [Verfasser], and Thomas [Akademischer Betreuer] Euler. "Identification of feedback mechanisms from horizontal cells to cone photoreceptors in the mouse retina using two‐photon calcium imaging and pharmacology / Robin Kemmler ; Betreuer: Thomas Euler." Tübingen : Universitätsbibliothek Tübingen, 2014. http://d-nb.info/1162971215/34.
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Doan, Thuy Anh. "Mammalian rod's single-photon responses : what do they tell us about rapid and reliable GPCR inactivation /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10638.
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Joyce, Daniel S. "Temporal, spatial and adaptation characteristics of melanopsin inputs to the human pupil light reflex." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/98495/14/Daniel_Joyce_Thesis.pdf.
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This thesis advanced understanding of the timing, spatial and adaptation properties of the human pupil light reflex (PLR). It developed new functional measures of the eye's melanopsin cells, which regulate circadian rhythms and pupil size, and are dysfunctional in a range of common eye and brain disorders. Measuring the PLR under different light stimulations, this research determined that melanopsin inputs to the pupil are independent of stimulus timing, but are sensitive to both stimulus spatial location and adaptation level. The outcomes introduce new frameworks for translating these objective biomarkers of melanopsin function into clinical tools for diagnosing and monitoring disease.
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Bonezzi, Paul J. "The development of outer retinal photoresponsivity and the effects of sensory deprivation." University of Akron / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=akron1602525875711526.
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Field, Gregory Darin. "The limits to absolute visual sensitivity /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/10552.
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Krylov, Dmitri M. "Guanylyl cyclase activating protein-1 and its regulation of retinal guanylyl cyclases : a study by molecular biological methods and a novel mass spectrometry based method /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/9259.
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López, del Hoyo Natalia. "Role of Guanylate Cyclase Activating Proteins in photoreceptor cells of the retina in health and disease." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/283566.
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In the last two decades, it has been done a thoroughly research about the role of Guanylate Cyclase Activating Proteins (GCAPs) in photoreceptor cells of the retina as activity regulators of Retinal Guanylate Cyclase (RetGC), which allow to restore cGMP levels to darkness ones when intracellular Ca2+ falls.
However, little is known about: a) ¿What determines GCAPs distribution within the cell?, b) ¿Which other functions GCAP proteins, GCAP1 and GCAP2, carry out at other cellular compartments different from the sensory one? and c) ¿How they cause cell death when they are mutated? In this study we want address these questions.
1. First of all, we own a mouse model that expresses a GCAP2 mutated form unable to bind Ca2+ (bEF-GCAP2). Other mutations described for GCAP1 and present in some autosomic dominant Cone Rod Dystrophies (adCORD), prevent Ca2+ binding to some of its EF-hand domains which produces the constitutive activation of RetGC, and consequently, high cGMP levels that result in toxicity for the cell. However, we observe that our model causes the death by other mechanism, as RetGC is not activated by GCAP2, because GCAP2 is retained in the inner segment and does not translocate to the sensory compartment. We want to identify interactions that GCAP2 establish differentially in this compartment and could be retaining it. We find out 14-3-3 family of proteins by mass-spectrometry and liquid chromatography. Furthermore, bEF-GCAP2 is abnormally phosphorylated in vivo and GCAP2 phosphorylation promotes its binding to 14-3-3 binding. We demonstrate that GCAP2 phosphorylation in residue serine 201 is the cause of its retention in the inner segment, avoiding its translocation to the outer segment, and when we mutate serine 201 into a glycine, this retention is reverted in vivo. Finally, we propose that GCAP2 phosphorylation and its binding to 14-3-3 is what retains GCAP2 in the inner segment, and this happens in a balance way during dark/light day cycles. When this system overloads will cause retinal degeneration by the formation of aggregates. We believe that mutations in GCAP2 or light conditions promoting GCAP2 accumulation in its Ca2+-free form in the inner segment of the cell, bring to cell death by GCAP2 conformational instability. Most important, we propose that this will also apply for genetic scenarios mimicking the effects to constant light exposure, the so called “equivalent-light” scenarios.
2. Secondly, as a result of the identification of GCAP2 interaction to RIBEYE (Venkatesan et al. 2010) the major component of synaptic ribbons in the photoreceptor cell terminal, we developed an ultrastructural study of the role that GCAP2 may play in this compartment. Through confocal and electronic microscopy we have demonstrated the presence of GCAP1 and GCAP2 in rod synaptic ribbons. However, GCAP1 and GCAP2 are not necessary during synaptic ribbons assembling and basic maintenance. As GCAP2 overexpression in the wildtype background (which means a higher GCAP2:GCAP1 ratio) promotes ribbons disassembling, we propose that GCAP2 may play a role mediating the morphological changes that take place in the synaptic ribbons in response to variations in [Ca2+].En las dos últimas décadas se ha investigado a fondo el papel que juegan las Proteínas Activadoras de Guanilato Ciclasa (GCAPs) en las células fotorreceptor de la retina como proteínas encargadas de regular la actividad de la Guanilato Ciclasa (GC). Sin embargo se sabe poco acerca de: a) ¿Qué determina la distribución de GCAPs en la célula?, b) ¿Qué otras funciones ejercen GCAP1 y GCAP2 en otros compartimentos celulares distintos al segmento sensorial? y c) ¿Cómo dan lugar a muerte celular cuando están mutadas? En este estudio hemos querido encarar estas preguntas. 1. En primer lugar, poseemos un modelo de ratón que expresa una forma mutante de GCAP2 que no une Ca2+ (bEF-GCAP2). A diferencia de otras mutaciones descritas para GCAP1, en que se ha observado que la muerte celular es producida por niveles tóxicos de cGMP, observamos que nuestro modelo produce la muerte celular por otro mecanismo en que GCAP2 se acumula en el segmento interno. Identificamos abundantemente las distintas isoformas de 14-3-3 como interactores diferenciales de bEF-GCAP2, que a su vez está anormalmente fosforilada in vivo. Tras una serie de experimentos para caracterizar esta interacción, proponemos que la fosforilación de GCAP2 y su unión a 14-3-3 retienen a GCAP2 en el segmento interno, y si este mecanismo se sobrecarga por a) mutaciones en GCAP2, b) condiciones de luz que promuevan la acumulación de GCAP2 en su forma libre de Ca2+ en el segmento interno o c) condiciones genéticas que mimeticen los efectos de exposición a luz prolongada, tendría lugar la degeneración de la retina por la formación de agregados debido a la inestabilidad conformacional de GCAP2. 2. En segundo lugar, tras la identificación de la interacción de GCAP2 con RIBEYE (Venkatesan et al. 2010), el componente mayoritario de las cintillas sinápticas de fotorreceptores, realizamos un estudio ultrastructural del papel que puede estar jugando GCAP2 en este compartimento mediante microscopia electrónica y confocal, demostrando la presencia de GCAP1 y GCAP2 en las cintillas sinápticas de bastones. GCAP1 y GCAP2 son prescindibles en el ensamblaje y mantenimiento básico de las cintillas sinápticas, pero la sobreexpresión de GCAP2 en el fenotipo salvaje, que incrementa el ratio GCAP2:GCAP1, promueve el desensamblaje de las cintillas. Proponemos que GCAP2 podría jugar un papel mediando cambios morfológicos en las cintillas sinápticas promovidas por cambios en [Ca2+].
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Ensslen, Sonya Emily Lesya. "The role of signaling via the receptor tyrosine phosphatase PTPmu in retinal development and axon guidance." Connect to online version, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1080835127.
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Gagliardi, Giuliana. "Generation and selection of photoreceptor precursors from human-induced pluripotent stem cells for cell therapy Generation of storable retinal organoids and retinal pigmented epithelium from adherent human iPS cells in xeno-free and feeder-free conditions Characterization and transplantation of CD73-positive photoreceptors isolated from human iPSC-derived retinal organoids." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS082.
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Les maladies dégénératives de la rétine représentent un défi majeur de santé publique pour lequel les techniques thérapeutiques restent aujourd’hui insuffisantes et limitées. L'une des approches les plus prometteuses est la thérapie cellulaire, c'est-à-dire le remplacement d’une typologie cellulaire spécifique. Dans ce contexte, les cellules souches pluripotentes pourraient être utilisées comme source illimitée de cellules rétiniennes. Le protocole développé par notre groupe pour la génération de photorécepteurs transplantables à partir de cellules souches induites à la pluripotence (iPSCs) a été adapté à des conditions compatibles avec les normes dites « Good Manufacturing Practice » (GMP) afin de passer rapidement à une application clinique. L'antigène de surface CD73 a été caractérisé comme un marqueur spécifique des photorécepteurs dérivés de iPSCs humaines. Nous avons développé une stratégie de tri basée sur le ciblage magnétique de CD73, qui permet d’obtenir une population homogène de photorécepteurs. Nous avons démontré l’absence du risque de développement de tumeur lié à la transplantation de ces cellules. Enfin, les cellules CD73-positives sont capables de survivre et acquérir un certain niveau de maturité après transplantation chez un modèle de dystrophie rétinienne. Bien que la compétence de cellules greffées à former de connections synaptiques fonctionnelles et à rétablir la fonction visuelle est encore à démontrer, ce travail apporte un nouvel outil pour l’utilisation de photorécepteurs dérivés de iPSCs humaines pour des applications thérapeutiques ainsi que pour l’étude des pathologies concernant les photorécepteursRetinal degenerative diseases represent a major public health challenge, for which there are currently no effective treatments. Cell therapy represent a promising therapeutic approach, consisting in specifically replacing degenerated cells with new cells. In this perspective, pluripotent stem cells could be used as an unlimited source of retinal cells. The work presented here aimed at contributing to the development of a cell therapy product for the treatment of photoreceptor degenerative diseases. We have demonstrated the possibility to generate and store retinal organoids from human induced pluripotent stem cells (iPSCs) using raw media complying with Good Manufacturing Practice (GMP). We have characterized the surface antigen CD73 as a marker of photoreceptors in human retinal organoids derived from human iPSCs. We have established a protocol based on the magnetic labelling of CD73-positive cells allowing for the separation of a homogenous population of photoreceptors. We could demonstrate their safety by showing the absence of tumor development upon transplantation of these cells in an immune-compromised host. Finally, CD73-positive cells had the ability to survive and to reach a certain degree of maturation in a dystrophic retinal environment. Although the ability of donor cells to establish functional synaptic connections and mediate a significant rescue of the visual function remains to be assessed, this work provides an advancement for the use of iPSC-derived photoreceptors in clinical applications and for the study of photoreceptor diseases
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Lam, Phuong T. "Crispr/cas9-mediated genome editing of human pluripotent stem cells to advance human retina regeneration research." Miami University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=miami1575372014701457.
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Posvar, Winston Blair. "Variation of Ocular Parameters in Young Normal Eyes." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1491991936735843.
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García-García, Diana. "Müller Cells and Retinal Regeneration : The Role of the Hippo/YAP Signaling Pathway Yap Haploinsufficiency Leads to Müller Cell Dysfunction and Late-Onset Cone Dystrophy Linking YAP to Müller Glia Quiescence Exit in the Degenerative Retina." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL068.
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Les maladies dégénératives de la rétine sont une des causes principales de cécité. Parmi les différentes stratégies thérapeutiques actuellement étudiées, notre équipe s’intéresse au potentiel régénératif de la rétine. Une source cellulaire d'intérêt sont les cellules de Müller, principal type de cellules gliales de la rétine capables de se réactiver en cas de dégénérescence, un processus appelé gliose réactive, et dans certaines espèces d’adopter des caractéristiques de cellules souches. Si un tel processus confère la capacité de régénérer la rétine chez les téléostéens, il est cependant largement inefficace chez les mammifères. Avoir une meilleure connaissance des mécanismes moléculaires sous-jacents pourrait aider à transformer leur potentiel de régénération en nouvelles stratégies thérapeutiques en condition pathologique de dégénérescence rétinienne. Dans ce contexte, mon laboratoire s'est focalisé sur l'effecteur terminal de la voie Hippo, le cofacteur de transcription YAP, dont il a été démontré qu'il stimule la régénération de plusieurs organes en cas de lésion. Dans la rétine, YAP est spécifiquement exprimé dans les cellules de Müller et son niveau d’expression augmente en cas de lésion. Cependant, sa fonction dans l'homéostasie rétinienne, et en particulier son rôle dans la régénération rétinienne, sont encore inconnus. La première partie de ma thèse visait donc à décrypter la fonction de YAP dans les cellules de Müller de souris dans des conditions physiologiques et pathologiques. Nous avons révélé que YAP joue un rôle central dans l'homéostasie des cellules de Müller et en tant que tel, est un acteur clé de la survie des cônes au cours du vieillissement. En cas de lésion rétinienne, nous avons montré que YAP est essentiel pour la réactivation des gènes du cycle cellulaire qui accompagne normalement la gliose réactive. Dans ce contexte, nous avons également trouvé une interaction fonctionnelle entre YAP et la voie de signalisation EGFR, suggérant une fonction de YAP en tant qu’intégrateur des réseaux de signalisation mis en jeu dans le contexte régénératif. J'ai également constaté que la suractivation de YAP est suffisante pour induire la reprogrammation des cellules de Müller de souris en cellules hautement prolifératives […]. Dans l'ensemble, ce travail met en évidence le rôle critique de YAP dans la sortie de quiescence des cellules de Müller chez les mammifères et révèle ainsi une cible potentielle pour la médecine régénérative. La deuxième partie de mon projet de doctorat naît des découvertes émergentes mettant en évidence les voies inflammatoires comme régulateurs du processus de régénération. […] De plus, des découvertes récentes sur le rôle de YAP dans la régulation du processus inflammatoire m’ont conduit à faire l'hypothèse qu'il pourrait jouer un rôle dans la relation entre l'inflammation et la régénération rétinienne. J'ai donc cherché à étudier le rôle joué par l'inflammation sur le comportement des cellules de Müller de souris, et à comprendre comment YAP s'inscrit dans cette interaction. J'ai découvert de manière inattendue qu'un contexte pro-inflammatoire établi par les cellules microgliales stimule la prolifération des cellules de Müller de souris dans des explants rétiniens. De plus, mes résultats ont montré que cet effet mitogène se produit de manière dépendante de YAP. Par ailleurs, j'ai découvert que l'effet de la surexpression de YAP sur la prolifération des cellules de Müller peut être potentialisé par un environnement pro-inflammatoire et aboli en cas d’ablation des microglies. Enfin, nous avons constaté que, à son tour, YAP régule des cytokines inflammatoires clés. Dans l'ensemble, cette partie de mon projet permet non seulement d’approfondir nos connaissances concernant l'impact de l'inflammation sur le comportement des cellules de Müller de la souris, mais met également en évidence YAP en tant qu'acteur clé dans la connexion entre l'inflammation et la régénération rétinienneDegenerative diseases of the retina are one of the main causes of blindness. Among the various therapeutic strategies currently being studied, our team is focusing on the regenerative potential of the retina. One cellular source of interest are Müller cells, the main type of glial cells in the retina capable of reactivating in case of degeneration, a process called reactive gliosis, and in some species adopting certain characteristics of stem cells. If such a process sustains powerful regeneration abilities in teleosts, it is however largely inefficient in mammals. Hence, increasing our knowledge of the molecular mechanisms underlying the behaviour of these cells under pathological conditions may help turning their regenerative properties into new therapeutic strategies. In this context, my laboratory focused on the terminal effector of the Hippo pathway, the co-transcriptional factor YAP, which has been shown to stimulate regeneration of several injured organs. In the retina, YAP is specifically expressed in Müller cells and upregulated in case of damage. However, its function in retinal homeostasis, and its role in retinal regeneration remained unknown.The first part of my PhD aimed at deciphering YAP function in mouse Müller cells in both physiological and pathological conditions. In essence, we revealed a central role of YAP in Müller cell-dependent retinal homeostasis and as such, as a key player for cone survival during aging. In case of retinal damage, we showed that YAP upregulation is critical for cell-cycle gene reactivation that normally accompanies reactive gliosis. In this context, we also found a functional interaction between YAP and the EGFR signaling pathway, supporting a function of YAP as a hub within the complex signaling network of key regenerative signaling pathways. I also found that YAP overactivation is sufficient to induce mouse Müller cell reprogramming into highly proliferative cells, mimicking a fish or amphibian condition, when Müller cells spontaneously proliferate upon injury. As a whole, this work highlights the critical role of YAP in driving mammalian Müller cells to exit quiescence and thus reveals a potential target for regenerative medicine.The second part of my PhD project stemmed from the emerging discoveries highlighting inflammatory pathways as regulators of the regenerative process. Although inflammation is considered to hamper retinal regeneration in mammals, there are no studies regarding the influence of inflammation on mouse Müller cell-dependent regenerative process. In addition, recent discoveries on the role of YAP in the regulation of the inflammatory process lead to the hypothesis that it could play a role in the relationship between inflammation and retinal regeneration. I thus aimed at investigating the role played by the injury-induced inflammation on mouse Müller cell behavior and how YAP fits in this interplay. I unexpectedly discovered that a microglial-dependent pro-inflammatory context stimulates mouse Müller cell proliferation in retinal explants. Importantly, my results showed that this mitogenic effect occurs in a YAP-dependent manner. Moreover, I uncovered that the effect of YAP overexpression on Müller cell proliferation can be potentiated by a pro-inflammatory environment, and abolished upon microglia depletion. Finally, we found that, in turn, YAP regulates key inflammatory cytokines. Altogether, this part of my project not only deepen our knowledge regarding the impact of inflammation on mouse Müller cell behavior, it also highlights YAP as a key player in the crosstalk between inflammation and retinal regeneration
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Chrysostomou, Vicki. "Cell biology of cone photoreceptors in the degenerating retina : damage, recovery and rod-dependence." Phd thesis, 2009. http://hdl.handle.net/1885/151392.
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Crespo, Catia. "Maturation of Photoreceptor Cells During Zebrafish Retinal Development." Doctoral thesis, 2017. https://tud.qucosa.de/id/qucosa%3A31130.
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Zebrafish have been used as a model to study the vertebrate retina due to its functional and structural similarities to the human retina. Photoreceptor cells (PRCs)
are highly specialised type of neurons present in the retina. In zebrafish, PRCs can
be divided into 5 different subtypes, rods and green, red, blue and UV sensitive cones. Mature PRCs are composed of different morphological compartments (basal domain, inner segment and outer segment), which are essential for their phototransduction
ability. During development, these cells are known to arise from columnar
neuroepithelium precursor cells and undergo a maturation process to become
compartmentalised10. However, a detailed characterisation of this process is lacking in zebrafish. In this project, I aimed to establish and characterise in detail the stages of
PRC maturation in zebrafish. Next, I aimed to investigate the role of candidate genes in this PRC maturation process.
To label the plasma membrane of all cells, a zebrafish transgenic line was utilised.
Furthermore, a novel zebrafish transgenic line that labels the outer segments of red
sensitive PRCs was generated. This transgenic line enabled visualisation and volume
quantification of outer segments of red sensitive cones. The use of both transgenic lines in combination with antibody stainings indicated that, from 72 hours post fertilisation (hpf) onwards, subtypes of PRCs exhibit differences in growth rate and morphology of their cell compartments. Additionally, differences in mitochondrial clusters and nuclei positioning were observed during the maturation process. From 72 hpf to 120 hpf, rough endoplasmic reticulum accumulation emerged specifically in rod like PRCs. Changes in chromatin organisation were observed in UV sensitive cones like PRCs from 120 hpf onwards. This showed that a high degree of complexity was observed even within the cone PRC subtypes. Lastly, the role of a candidate gene, crb2b, was examined by comparing PRC maturation process in WT and crb2b mutants. My results indicate that loss of Crb2b does not show obvious defects in PRC maturation.
Results obtained in this dissertation provided a comprehensive characterisation of
six independent PRC maturation stages using the criteria of cell compartmentalisation
and growth, organellar distribution and localisation of cell polarity related protein
complexes. This defined developmental timeline provides a platform to further study
PRC maturation and function.
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"Apoptosis of photoreceptor cells in the early stage of iron-induced retinal degeneration." 1997. http://library.cuhk.edu.hk/record=b5889292.
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Wang Zhi-Jun.Thesis (M.Phil.)--Chinese University of Hong Kong, 1997.
Includes bibliographical references (leaves 54-63).
ABSTRACT --- p.VI
Chapter I. --- INTRODUCTION --- p.1
Chapter A. --- Literature review --- p.1
Chapter 1. --- Retinal iron toxicity --- p.2
Clinical siderotic retinopathy --- p.2
Experimental siderotic retinopathy --- p.4
Free radical involvement in siderotic retinopathy --- p.5
Chapter 2. --- Experimental photic retinopathy in rats --- p.8
Morphologic features --- p.8
Free radical involvement in photic retinopathy --- p.9
Chapter 3. --- Mechanisms of cell death --- p.9
Necrosis --- p.10
Apoptosis --- p.10
Chapter B. --- Statement of the problems --- p.15
Chapter II. --- MATERIALS AND METHODS --- p.17
Chapter A. --- Siderotic retinopathy model --- p.17
Animals --- p.17
Reagents and equipment --- p.18
Surgical procedures --- p.18
Chapter B. --- Histochemical methods --- p.18
Reagents and equipment --- p.19
Paraffin sections --- p.19
H&E staining --- p.19
TUNEL technique --- p.20
Schmeltzer's iron staining --- p.21
Chinoy's ascorbic acid staining --- p.21
Chapter C. --- Biochemical methods --- p.21
Reagents and equipment --- p.22
DNA gel electrophoresis --- p.22
Analysis of ascorbic acid and uric acid --- p.23
Chapter III. --- RESULTS --- p.24
Chapter A. --- Observations in rats --- p.24
Morphologic changes after H&E staining --- p.24
Visualization of apoptosis by TUNEL technique --- p.25
Internucleosomal DNA fragmentation --- p.26
Negative staining of iron in the ONL --- p.27
Positive staining of ascorbic acid in the ONL --- p.27
Chapter B. --- Observations in rabbits --- p.27
Positive staining of ascorbic acid in all retinal layers --- p.27
Apoptosis occurred in all retinal layers --- p.28
Changes of ascorbic acid and uric acid after iron implantatio --- p.28
Chapter IV. --- DISCUSSION --- p.48
Chapter V. --- CONCLUSION --- p.53
References --- p.54
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Tran, Thanh Tan. "Retinal degeneration in and in vivo electroretinography measurements of Smoky Joe Chickens." Thesis, 2012. http://hdl.handle.net/10012/7068.
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Inherited retinal degenerative diseases can affect various components of the retina leading to blindness. Five different mutant strains of chicken have been studied extensively as potential models for inherited retinal degeneration. The Smoky Joe (SJ) chicken is a sixth genetically blind strain of White Leghorns that shows various degrees of blindness at hatch and by 8 weeks post-hatch, have complete blindness for those that are homozygous. The objective of this study was to characterize the retinal degeneration in these birds by histology, both during embryonic and post-hatch development, and to the retinal function using electroretinograms (ERG). For both embryonic and post-hatch development, a significantly lower number of cells were found in the retina of blind birds compared to sighted (both p<0.0001). The significant contributor to cell number decrease was the loss of amacrine cells located in the inner nuclear layer. Photoreceptors were also found to potentially decrease in number, but at a later stage. ERG recordings revealed decreases in amplitudes of b-waves and oscillatory potentials in blind birds, but not in sighted. Both histology and ERG findings support the idea that the inner retinal cells are affected. The results indicate that degeneration in the Smoky Joe retina occurs mostly within the inner nuclear layer affecting amacrine cells. This hampers the functional capacity of the retina, causing blindness.
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Anjos, Pedro Filipe dos Santos. "Development of a fundus camera for analysis of photoreceptor directionality in the healthy retina." Master's thesis, 2015. http://hdl.handle.net/10362/15618.
Full textAbstract:
The Stiles-Crawford effect (SCE) is the well-known phenomenon in which the brightness of light perceived by the human eye depends upon its entrance point in the pupil. This physiological characteristic is due to the directional sensitivity of the cone photoreceptors in the retina and it displays an approximately Gaussian dependency which is altered in a number of pathologies. Retinal imaging, a widely spread clinical practice, may be used to evaluate the SCE and thus serve as diagnostic tool. Nonetheless, its use for such a purpose is still underdeveloped and far from the clinical reality.
In this project a fundus camera was built and used to assess the cone photoreceptor directionality by reflective imaging of the retina in healthy individuals. The physical and physiological implications of its development are addressed in detail in the text: the optical properties of the human eye, illumination issues, acquiring a retinal image formed by the eye, among others. A full description of the developmental process that led to the final measuring method and results is also given.
The developed setup was successfully used to obtain high quality images of the eye fundus and in particular the parafoveal cone photoreceptors. The SCE was successfully observed and characterized. Even though considerable improvements could be done to the measurement method, the project showed the feasibility of using retinal imaging to evaluate the SCE thus motivating its usage in a clinical environment.
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Ching-AnKao and 高慶安. "Activation by AUY-922, an Inhibitor of HSP-90, of Non-Selective Cation Currents in Retinal Photoreceptor-Derived Cells(661W)." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/22746531727034473363.
Full textAbstract:
碩士國立成功大學
生理學研究所
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NVP-AUY922 (AUY) is currently recognized as a potent inhibitor of heat shock protein-90 (HSP-90). HSP-90, the most abundant molecular chaperone, is recognized to be essential for cell survival, proliferation, and apoptosis. HSP-90 is an important target for cancer therapeutics because tumor cells exist in a stressful environment and need depend on HSP-90 to grow and survive. Most importantly, the HSP-90 inhibitors such as AUY are thought to have strong therapeutic potential in a wide variety of tumor types, including solid tumors. However, AUY appears to possess an additional effect that does not require inhibition of HSP-90. Despite its inhibitory effect on HSP-90 activity, there are some adverse effects of this compound including ocular toxicities. The precise mechanism of action of AUY-induced ocular damage is still poorly understood. Therefore, in this study, we sought to investigate the possible effects of AUY and other related compounds on ion channels in a photoreceptor cell line (661W). The patch-clamp technique was used to evaluate electrophysiological properties of 661W photoreceptor cells. In whole-cell model, AUY increases the amplitude of non-selective (NS) cation current (INS) in a concentration-dependent fashion with an EC50 value of 1.7 μM. Neither iberiotoxin (200 nM) nor apamin (200 nM) had any effects on AUY-induced INS, while LaCl3 (100 μM) reversed it significantly. 17-AAG (3 μM) or BIIB021 (3 μM) increased the INS amplitude. AUY slowed the time course of INS inactivation elicited by membrane hyperpolarization. In cell-attached recordings, when AUY was applied to the bath, the activity of NS cation channels was significantly elevated with no change in single-channel conductance. With long-lasting ramp pulse protocol, addition of AUY produced a left shift in the activation curve of NS channels by 18 mV, with no change in the slope factor of the curve. The probability of NS-channel openings enhanced by AUY was decreased by LaCl3 (100 μM), while it was increased by BAPTA-AM (10 μM). AUY (10 μM) also suppressed L-type Ca2+ current with no change in the current-voltage relationship of this current. Under current-clamp conditions, addition of AUY caused membrane depolarization. In cells transfected with TRPM3 siRNAs, NS-channel activity was diminished. AUY-mediated stimulation of INS is unlinked to its inhibition of HSP-90 activity. Therefore, AUY interacts directly with the TRPM3 channel to increase INS and subsequently to depolarize the membrane in these cells. Taken together, our results suggested that TRPM3-encoded NS channels are primarily responsible for generation of INS in 661W cells. In conclusion, constitutive activation of these channels may play crucial roles in AUY-induced changes in visual acuity.
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Shi, Zhiwei. "The role of Vsxl in the development of cone bipolar cells in mouse retina." Thesis, 2010. http://hdl.handle.net/1828/3652.
Full textAbstract:
Visual system homeobox 1 (Vsx1) is a paired-like:CVC homeodomain
transcription factor that is expressed in a subset of retinal bipolar cells. Vsx1-null mice
have previously been shown to have defects in bipolar cell terminal differentiation
characterized by the reduced expression of four OFF bipolar cell-specific markers and
electrophysiological defects in the OFF visual signaling pathway. The availability of
recently identified bipolar cell markers enables a further characterization of the Vsx1-null
mutant. I determined that Vsx1 is expressed in Type 7 ON bipolar cells and observed the
upregulation of three cell markers: Cabp5, Chx10, and alpha-gustducin:GFP in this cell
type in Vsx1-null mice. These data reveal a trend in which Vsx1 functions as a
transcriptional repressor in Type 7 ON bipolar cells and as an activator in Type 2 OFF
bipolar cells. Lastly, my data indicate that Vsx1 is required for the expression of two
Type 3a bipolar cell markers, however, the mechanism by which it does so appears to be
complex, as I was unable to detect Vsx1 protein or reporter gene expression in this cell
type.Graduate
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Llonch, Silvia. "Photoreceptor transplantation into the mammalian retina: new perspectives in donor-host interaction." 2018. https://tud.qucosa.de/id/qucosa%3A70607.
Full textAbstract:
Human senses are specifically designed to recognize and understand the world that surrounds us. Even though we have five senses, vision alone is responsible for at least 30 % of the sensory input to our brain. The visual process is initiated in a highly specialized cell type, the photoreceptors. These are light-sensitive cells located in the retina, a layered nervous tissue situated at the back of the eye. Retinal degeneration diseases are a highly heterogeneous group of conditions that include mutations affecting the survival, maintenance and proper functioning of photoreceptors or the adjacent retinal pigment epithelium (RPE). Such mutations, alone or in combination with environmental factors, cause the loss of the affected cells, and therefore, impairment of the visual sense. Retinitis Pigmentosa and Age-related Macular Degeneration are typical examples of retinal degenerative diseases eventually leading to blindness. In the first one, rod photoreceptors degenerate and consequently also cone photoreceptors are lost. The second is characterized by malfunction and loss of both, RPE and photoreceptor cells. Many current therapeutic approaches for the treatment of retinal degenerative diseases focus on slowing down the progression of the disease, rather than restoring the visual function. Currently, new therapies with the potential to recover the visual signal are under development. Some of these therapeutic strategies have already reached clinical stages, including gene therapy or retinal prosthesis. However, gene therapy approaches require the presence of remaining photoreceptors and, furthermore, particular targeting of disease-related genes. Retinal prosthesis still require improvement in terms of long-term biocompatibility and relevant visual function recovery. An alternative strategy for vision restoration is cell replacement of the lost photoreceptors, which is potentially suitable for targeting late stages of retinal degeneration diseases, independently of the inherent cause of the disease. Human vision relies primarily on cone photoreceptors, which are the cells responsible for color and high acuity vision under daylight conditions. However, cones represent a minority of the photoreceptors within the retina, and so, due to the low availability of these cells, cone photoreceptor transplantation studies lag behind rod transplantation studies. Consequently, in this study, strategies to increase the numbers of cone photoreceptors within mouse embryonic stem cells (mESC)-derived retinal organoids, which represent a potential cell source for transplantation studies, were explored. In this regard, I manipulated developmental pathways known to be involved in retinal development, such as Notch signaling, through the addition of various compounds in the retinal organoid maturation media. However, early cone markers have not yet been definitively identified, complicating the detection and isolation of cone photoreceptor precursors within the organoids. Therefore, a new early cone-reporter mESC line was generated in the course of this study as a valuable tool with the potential to facilitate the development of novel cone photoreceptor replacement therapies. Equally important in the field of photoreceptor cell replacement is the understanding of how the transplanted donor cells interact with the host retina. Previous studies have shown that visual function improvement is possible after transplanting rod or cone-like photoreceptor precursors into the sub-retinal space of mouse models for retinal degeneration. For many years it has been assumed that the underlying mechanism for the observed vision improvement was the migration and structural integration of donor cells into the host outer nuclear layer, where they mature and establish synaptic connections with the host retinal circuitry. However, experiments performed in this study demonstrate, for the first time, that upon transplantation donor and host photoreceptors exchange cytoplasmic material rather than structurally integrate into the host outer nuclear layer. Furthermore, insights into the transferred cytoplasmic content are given, i.e. that mRNA, but not mitochondria are exchanged by donor and host photoreceptors. This novel way of photoreceptor-photoreceptor communication led to a paradigm change in the field of retinal transplantation, requiring a re-interpretation of former transplantation studies. In addition, the discovery of the material transfer phenomenon might serve as a starting point for the development of novel therapeutic strategies based on cell-cell support for the treatment of retinal degenerative diseases.
This study generated new knowledge in two important topics related to the development of cell therapies for retinal degeneration diseases, including the development of tools for cone transplantation studies as well as elucidating the interaction between donor and host cells upon transplantation.