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Medecine Sciences : M/S 2020The neuroretina is a functional unit of the central nervous system that converts a light signal into a nerve impulse. Of neuroectodermal origin, derived from the... (Review)
Review
The neuroretina is a functional unit of the central nervous system that converts a light signal into a nerve impulse. Of neuroectodermal origin, derived from the diencephalon, the neuroretina is a layered tissue composed of six types of neuronal cells (two types of photoreceptors: cones and rods, horizontal, bipolar, amacrine and ganglion cells) and three types of glial cells (Müller glial cells, astrocytes and microglial cells). The neuroretina lays on the retinal pigmentary epithelium, that together form the retina. The existence of the internal and external blood-retinal barriers and intra-retinal junctions reflects the fineness of regulation of the retinal exchanges with the circulation and within the retina itself. The central zone of the human retina, which is highly specialized for visual acuity, has anatomical specificities. Recent imaging methods make it possible now to enrich our knowledge of the anatomical and functional characteristics of the retina, which are still imperfectly described.
Topics: Animals; Choroid; Humans; Neuroglia; Retina; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Rod Photoreceptor Cells; Retinal Vessels
PubMed: 32614310
DOI: 10.1051/medsci/2020094 -
Progress in Retinal and Eye Research Mar 2023The light sensor of vertebrate scotopic (low-light) vision, rhodopsin, is a G-protein-coupled receptor comprising a polypeptide chain with bound chromophore,... (Review)
Review
The light sensor of vertebrate scotopic (low-light) vision, rhodopsin, is a G-protein-coupled receptor comprising a polypeptide chain with bound chromophore, 11-cis-retinal, that exhibits remarkable physicochemical properties. This photopigment is extremely stable in the dark, yet its chromophore isomerises upon photon absorption with 70% efficiency, enabling the activation of its G-protein, transducin, with high efficiency. Rhodopsin's photochemical and biochemical activities occur over very different time-scales: the energy of retinaldehyde's excited state is stored in <1 ps in retinal-protein interactions, but it takes milliseconds for the catalytically active state to form, and many tens of minutes for the resting state to be restored. In this review, we describe the properties of rhodopsin and its role in rod phototransduction. We first introduce rhodopsin's gross structural features, its evolution, and the basic mechanisms of its activation. We then discuss light absorption and spectral sensitivity, photoreceptor electrical responses that result from the activity of individual rhodopsin molecules, and recovery of rhodopsin and the visual system from intense bleaching exposures. We then provide a detailed examination of rhodopsin's molecular structure and function, first in its dark state, and then in the active Meta states that govern its interactions with transducin, rhodopsin kinase and arrestin. While it is clear that rhodopsin's molecular properties are exquisitely honed for phototransduction, from starlight to dawn/dusk intensity levels, our understanding of how its molecular interactions determine the properties of scotopic vision remains incomplete. We describe potential future directions of research, and outline several major problems that remain to be solved.
Topics: Photoreceptor Cells; Retina; Rhodopsin; Transducin; Vision, Ocular; Animals
PubMed: 36273969
DOI: 10.1016/j.preteyeres.2022.101116 -
Revue Medicale de Liege Feb 2020Retinitis pigmentosa is the most frequent hereditary dystrophy of the retina, with a global prevalence of 1/4.000. The underlying mechanism involves progressive loss,...
Retinitis pigmentosa is the most frequent hereditary dystrophy of the retina, with a global prevalence of 1/4.000. The underlying mechanism involves progressive loss, first of the rod photoreceptor cells, followed by the cone photoreceptor cells. Finally, complete blindness may occur. Genetic transmission is known but most cases are sporadic. Few effective treatments exist nowadays and hence regular follow-up is required in a revalidation center.
Topics: Humans; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa
PubMed: 32030928
DOI: No ID Found -
Annual Review of Vision Science Sep 2021The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O, glucose, and other nutrients diffuse out of the choroid and then filter... (Review)
Review
The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O, glucose, and other nutrients diffuse out of the choroid and then filter through a monolayer of retinal pigment epithelium (RPE) cells to fuel the retina. Recent studies of energy metabolism have revealed striking differences between retinas and RPE cells in the ways that they extract energy from fuels. The purpose of this review is to suggest and evaluate the hypothesis that the retina and RPE have complementary metabolic roles that make them depend on each other for survival and for their abilities to perform essential and specialized functions.
Topics: Choroid; Energy Metabolism; Retina; Retinal Pigment Epithelium
PubMed: 34102066
DOI: 10.1146/annurev-vision-100419-115156 -
The FEBS Journal Feb 2023The blood-retina barrier (BRB) is the term used to define the properties of the retinal capillaries and the retinal pigment epithelium (RPE), which separate the systemic... (Review)
Review
The blood-retina barrier (BRB) is the term used to define the properties of the retinal capillaries and the retinal pigment epithelium (RPE), which separate the systemic circulation from the retina. More specifically, the inner blood-retina barrier (iBRB) is used to describe the properties of the endothelial cells that line the microvasculature of the inner retina, while the outer blood-retina barrier (oBRB) refers to the properties of the RPE cells that separate the fenestrated choriocapillaris from the retina. The BRB is not a fixed structure; rather, it is dynamic, with its components making unique contributions to its function and structural integrity, and therefore the retina. For example, while tight junction (TJ) proteins between retinal endothelial cells are the key molecular structures in the maintenance of the iBRB, other cell types surrounding endothelial cells are also important. In fact, this overall structure is termed the neurovascular unit (NVU). The integrity of the BRB is crucial in the maintenance of a 'dry', tightly regulated retinal microenvironment through the regulation of transcellular and paracellular transport. Specifically, breakdown of TJs can result in oedema formation, a hallmark feature of many retinal diseases. Here, we will describe the oBRB briefly, with a more in-depth focus on the structure and function of the iBRB in health and diseased states. Finally, the contribution of the BRB to the pathophysiology of age-related macular degeneration (AMD), diabetic retinopathy (DR) and other rarer retinal diseases will be discussed.
Topics: Humans; Endothelial Cells; Blood-Retinal Barrier; Retina; Retinal Diseases; Retinal Pigment Epithelium
PubMed: 34923749
DOI: 10.1111/febs.16330 -
Progress in Retinal and Eye Research Sep 2023Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of the highest metabolic rates body-wide and is constantly... (Review)
Review
Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of the highest metabolic rates body-wide and is constantly exposed to photooxidative damage and external stressors. Mitophagy is the selective autophagic degradation of mitochondria within lysosomes, and can be triggered by distinct stimuli such as mitochondrial damage or hypoxia. Here, we review the importance of mitophagy in retinal physiology and pathology. In the developing retina, mitophagy is essential for metabolic reprogramming and differentiation of retina ganglion cells (RGCs). In basal conditions, mitophagy acts as a quality control mechanism, maintaining a healthy mitochondrial pool to meet cellular demands. We summarize the different autophagy- and mitophagy-deficient mouse models described in the literature, and discuss the potential role of mitophagy dysregulation in retinal diseases such as glaucoma, diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration. Finally, we provide an overview of methods used to monitor mitophagy in vitro, ex vivo, and in vivo. This review highlights the important role of mitophagy in sustaining visual function, and its potential as a putative therapeutic target for retinal and other diseases.
Topics: Mice; Animals; Mitophagy; Retina; Retinal Ganglion Cells; Autophagy; Mitochondria; Homeostasis
PubMed: 37454969
DOI: 10.1016/j.preteyeres.2023.101205 -
American Journal of Ophthalmology Aug 2021To determine classification criteria for acute retinal necrosis (ARN).
PURPOSE
To determine classification criteria for acute retinal necrosis (ARN).
DESIGN
Machine learning of cases with ARN and 4 other infectious posterior uveitides / panuveitides.
METHODS
Cases of infectious posterior uveitides / panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set.
RESULTS
Eight hundred three cases of infectious posterior uveitides / panuveitides, including 186 cases of ARN, were evaluated by machine learning. Key criteria for ARN included (1) peripheral necrotizing retinitis and either (2) polymerase chain reaction assay of an intraocular fluid specimen positive for either herpes simplex virus or varicella zoster virus or (3) a characteristic clinical appearance with circumferential or confluent retinitis, retinal vascular sheathing and/or occlusion, and more than minimal vitritis. Overall accuracy for infectious posterior uveitides / panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for ARN were 15% in the training set and 11.5% in the validation set.
CONCLUSIONS
The criteria for ARN had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
Topics: Adult; Female; Fluorescein Angiography; Fundus Oculi; Humans; Machine Learning; Male; Middle Aged; Retina; Retinal Necrosis Syndrome, Acute; Tomography, Optical Coherence
PubMed: 33845012
DOI: 10.1016/j.ajo.2021.03.057 -
International Journal of Molecular... Sep 2019Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of... (Review)
Review
Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of prolonged hyperglycemia and is characterized by leaky retinal vasculature, retinal ischemia, retinal inflammation, angiogenesis, and neovascularization. The number of DR patients is growing with an increase in the elderly population, and therapeutic approaches are limited, therefore, new therapies to prevent retinal injury and enhance repair are a critical unmet need. Besides vascular endothelial growth factor (VEGF)-induced vascular proliferation, several other mechanisms are important in the pathogenesis of diabetic retinopathy, including vascular inflammation. Thus, combining anti-VEGF therapy with other new therapies targeting these pathophysiological pathways of DR may further optimize treatment outcomes. Technological advancements have allowed for high-throughput proteomic studies examining biofluids such as aqueous humor, vitreous humor, tear, and serum. Many DR biomarkers have been identified, especially proteins involved in retinal inflammatory processes. This review attempts to summarize the proteomic biomarkers of DR-associated retinal inflammation identified over the last several years.
Topics: Biomarkers; Body Fluids; Diabetic Retinopathy; Humans; Protein Processing, Post-Translational; Proteome; Proteomics; Retinitis
PubMed: 31557880
DOI: 10.3390/ijms20194755 -
Nature Medicine Mar 2020Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people....
Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.
Topics: Adult; Eye Proteins; Genetic Diseases, X-Linked; Genetic Therapy; Humans; Middle Aged; Mutation; Retina; Retinitis Pigmentosa; Young Adult
PubMed: 32094925
DOI: 10.1038/s41591-020-0763-1 -
International Journal of Molecular... Jan 2022Brain plasticity is a well-established concept designating the ability of central nervous system (CNS) neurons to rearrange as a result of learning, when adapting to... (Review)
Review
Brain plasticity is a well-established concept designating the ability of central nervous system (CNS) neurons to rearrange as a result of learning, when adapting to changeable environmental conditions or else while reacting to injurious factors. As a part of the CNS, the retina has been repeatedly probed for its possible ability to respond plastically to a variably altered environment or to pathological insults. However, numerous studies support the conclusion that the retina, outside the developmental stage, is endowed with only limited plasticity, exhibiting, instead, a remarkable ability to maintain a stable architectural and functional organization. Reviewed here are representative examples of hippocampal and cortical paradigms of plasticity and of retinal structural rearrangements found in organization and circuitry following altered developmental conditions or occurrence of genetic diseases leading to neuronal degeneration. The variable rate of plastic changes found in mammalian retinal neurons in different circumstances is discussed, focusing on structural plasticity. The likely adaptive value of maintaining a low level of plasticity in an organ subserving a sensory modality that is dominant for the human species and that requires elevated fidelity is discussed.
Topics: Animals; Cell Plasticity; Humans; Neuronal Plasticity; Retina; Retinal Neurons
PubMed: 35163059
DOI: 10.3390/ijms23031138