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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 -
Cellular and Molecular Life Sciences :... Oct 2021Inherited retinal diseases (IRDs) cause progressive loss of light-sensitive photoreceptors in the eye and can lead to blindness. Gene-based therapies for IRDs have shown... (Review)
Review
Inherited retinal diseases (IRDs) cause progressive loss of light-sensitive photoreceptors in the eye and can lead to blindness. Gene-based therapies for IRDs have shown remarkable progress in the past decade, but the vast majority of forms remain untreatable. In the era of personalised medicine, induced pluripotent stem cells (iPSCs) emerge as a valuable system for cell replacement and to model IRD because they retain the specific patient genome and can differentiate into any adult cell type. Three-dimensional (3D) iPSCs-derived retina-like tissue called retinal organoid contains all major retina-specific cell types: amacrine, bipolar, horizontal, retinal ganglion cells, Müller glia, as well as rod and cone photoreceptors. Here, we describe the main applications of retinal organoids and provide a comprehensive overview of the state-of-art analysis methods that apply to this model system. Finally, we will discuss the outlook for improvements that would bring the cellular model a step closer to become an established system in research and treatment development of IRDs.
Topics: Animals; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Neuroglia; Organoids; Retina; Retinal Diseases; Retinal Rod Photoreceptor Cells
PubMed: 34420069
DOI: 10.1007/s00018-021-03917-4 -
Sub-cellular Biochemistry 2016Visual systems detect light by monitoring the effect of photoisomerization of a chromophore on the release of a neurotransmitter from sensory neurons, known as rod and... (Review)
Review
Visual systems detect light by monitoring the effect of photoisomerization of a chromophore on the release of a neurotransmitter from sensory neurons, known as rod and cone photoreceptor cells in vertebrate retina. In all known visual systems, the chromophore is 11-cis-retinal complexed with a protein, called opsin, and photoisomerization produces all-trans-retinal. In mammals, regeneration of 11-cis-retinal following photoisomerization occurs by a thermally driven isomerization reaction. Additional reactions are required during regeneration to protect cells from the toxicity of aldehyde forms of vitamin A that are essential to the visual process. Photochemical and phototransduction reactions in rods and cones are identical; however, reactions of the rod and cone visual pigment regeneration cycles differ, and perplexingly, rod and cone regeneration cycles appear to use different mechanisms to overcome the energy barrier involved in converting all-trans- to 11-cis-retinoid. Abnormal processing of all-trans-retinal in the rod regeneration cycle leads to retinal degeneration, suggesting that excessive amounts of the retinoid itself or its derivatives are toxic. This line of reasoning led to the development of various approaches to modifying the activity of the rod visual cycle as a possible therapeutic approach to delay or prevent retinal degeneration in inherited retinal diseases and perhaps in the dry form of macular degeneration (geographic atrophy). In spite of great progress in understanding the functioning of rod and cone regeneration cycles at a molecular level, resolution of a number of remaining puzzling issues will offer insight into the amelioration of several blinding retinal diseases.
Topics: Animals; Carrier Proteins; Darkness; Forecasting; Geographic Atrophy; Humans; Isomerism; Light; Molecular Structure; Photochemistry; Photons; Pregabalin; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Pigments; Retinal Rod Photoreceptor Cells; Retinaldehyde; Schiff Bases; Vertebrates; Vision, Ocular; Vitamin A; cis-trans-Isomerases
PubMed: 27830507
DOI: 10.1007/978-94-024-0945-1_9 -
Eye (London, England) Feb 2016Under twenty-first-century metropolitan conditions, almost all of our vision is mediated by cones and the photopic system, yet cones make up barely 5% of our retinal... (Review)
Review
Under twenty-first-century metropolitan conditions, almost all of our vision is mediated by cones and the photopic system, yet cones make up barely 5% of our retinal photoreceptors. This paper looks at reasons why we additionally possess rods and a scotopic system, and asks why rods comprise 95% of our retinal photoreceptors. It considers the ability of rods to reliably signal the arrival of individual photons of light, as well as the ability of the retina to process these single-photon signals, and it discusses the advantages that accrue. Drawbacks in the arrangement, including the very slow dark adaptation of scotopic vision, are also considered. Finally, the timing of the evolution of cone and rod photoreceptors, the retina, and the camera-style eye is summarised.
Topics: Animals; Color Vision; Contrast Sensitivity; Dark Adaptation; Humans; Light; Night Vision; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Vision, Ocular
PubMed: 26563661
DOI: 10.1038/eye.2015.236 -
Pflugers Archiv : European Journal of... Sep 2021In the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract... (Review)
Review
In the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.
Topics: Animals; Gap Junctions; Humans; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Synapses
PubMed: 33988778
DOI: 10.1007/s00424-021-02572-9 -
Methods in Cell Biology 2015Retina is a neurosensory tissue lining the back of the eye and is responsible for light detection and relaying the signal to the visual cortex in the brain. Mammalian...
Retina is a neurosensory tissue lining the back of the eye and is responsible for light detection and relaying the signal to the visual cortex in the brain. Mammalian retina consists of six major types of neurons (including photoreceptors; rods and cones) and one type of glial cells arranged in distinct layers. Photoreceptors are the most abundant cell types accounting for approximately 60% of all cells in the retina. Owing to their unique structure and function as ciliated neurons and their vast majority, dysfunction and degeneration of photoreceptors is associated with several inherited blindness disorders, such as retinitis pigmentosa, cone-rod degeneration, and age-related macular degeneration. Therefore, it is imperative to examine the structure and function of photoreceptors so that better understanding of the pathogenesis of associated diseases can be obtained for designing therapeutic modalities. In this chapter, we will provide detailed methods for analyzing photoreceptor function (electroretinography), structure, and biochemical analysis of sensory cilia of photoreceptors using mammalian retina as model system. These methods are widely used to assess photoreceptor development and degeneration during disease.
Topics: Animals; Cilia; Electrophysiological Phenomena; Electroretinography; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Staining and Labeling
PubMed: 25837387
DOI: 10.1016/bs.mcb.2014.12.005 -
Progress in Retinal and Eye Research Nov 2016The rod cell has an extraordinarily specialized structure that allows it to carry out its unique function of detecting individual photons of light. Both the structural... (Review)
Review
The rod cell has an extraordinarily specialized structure that allows it to carry out its unique function of detecting individual photons of light. Both the structural features of the rod and the metabolic processes required for highly amplified light detection seem to have rendered the rod especially sensitive to structural and metabolic defects, so that a large number of gene defects are primarily associated with rod cell death and give rise to blinding retinal dystrophies. The structures of the rod, especially those of the sensory cilium known as the outer segment, have been the subject of structural, biochemical, and genetic analysis for many years, but the molecular bases for rod morphogenesis and for cell death in rod dystrophies are still poorly understood. Recent developments in imaging technology, such as cryo-electron tomography and super-resolution fluorescence microscopy, in gene sequencing technology, and in gene editing technology are rapidly leading to new breakthroughs in our understanding of these questions. A summary is presented of our current understanding of selected aspects of these questions, highlighting areas of uncertainty and contention as well as recent discoveries that provide new insights. Examples of structural data from emerging imaging technologies are presented.
Topics: Cryoelectron Microscopy; Humans; Membrane Proteins; Morphogenesis; Retinal Diseases; Retinal Rod Photoreceptor Cells
PubMed: 27352937
DOI: 10.1016/j.preteyeres.2016.06.002 -
Molecular Neurodegeneration Mar 2023Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in...
BACKGROUND
Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR.
METHODS
We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation.
RESULTS
PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration.
CONCLUSION
Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity.
Topics: Humans; Oxidative Phosphorylation; Retinal Degeneration; Glucose; Hypoxia; Lactic Acid; Retinal Rod Photoreceptor Cells
PubMed: 36882871
DOI: 10.1186/s13024-023-00602-x -
EBioMedicine Jan 2021Inherited retinal diseases (IRDs) were first classified clinically by history, ophthalmoscopic appearance, type of visual field defects, and electroretinography (ERG).... (Review)
Review
Inherited retinal diseases (IRDs) were first classified clinically by history, ophthalmoscopic appearance, type of visual field defects, and electroretinography (ERG). ERGs isolating the two major photoreceptor types (rods and cones) showed some IRDs with greater cone than rod retinal dysfunction; others were the opposite. Within the cone-rod diseases, there can be phenotypic variability, which can be attributed to genetic heterogeneity and the variety of visual function mechanisms that are disrupted. Most cause symptoms from childhood or adolescence, although others can manifest later in life. Among the causative genes for cone-rod dystrophy (CORD) are those encoding molecules in phototransduction cascade activation and recovery processes, photoreceptor outer segment structure, the visual cycle and photoreceptor development. We review 11 genes known to cause cone-rod disease in the context of their roles in normal visual function and retinal structure. Knowledge of the pathobiology of these genetic diseases is beginning to pave paths to therapy.
Topics: Age of Onset; Alleles; Genetic Association Studies; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Genotype; Humans; Mutation; Phenotype; Retinal Diseases; Retinal Rod Photoreceptor Cells; Vision, Ocular; Visual Acuity
PubMed: 33421946
DOI: 10.1016/j.ebiom.2020.103200 -
The Journal of Physiology Nov 2022The detection of light in the vertebrate retina utilizes a duplex system of closely related rod and cone photoreceptors: cones respond extremely rapidly, and operate at... (Review)
Review
The detection of light in the vertebrate retina utilizes a duplex system of closely related rod and cone photoreceptors: cones respond extremely rapidly, and operate at 'photopic' levels of illumination, from moonlight upwards; rods respond much more slowly, thereby obtaining greater sensitivity, and function effectively only at 'scotopic' levels of moonlight and lower. Rods and cones employ distinct isoforms of many of the proteins in the phototransduction cascade, and they thereby represent a unique evolutionary system, whereby the same process (the detection of light) uses a distinct set of genes in two classes of cell. The molecular mechanisms of phototransduction activation are described, and the classical quantitative predictions for the onset phase of the electrical response to light are developed. Recent work predicting the recovery phase of the rod's response to intense flashes is then presented, that provides an accurate account of the time that the response spends in saturation. Importantly, this also provides a new estimate for the rate at which a single rhodopsin activates molecules of the G-protein, transducin, that is substantially higher than other estimates in the literature. Finally, the evolutionary origin of the phototransduction proteins in rods and cones is examined, and it is shown that most of the rod/cone differences were established at the first of the two rounds of whole-genome duplication more than 500 million years ago.
Topics: Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Transducin; Retina; Light Signal Transduction
PubMed: 35412676
DOI: 10.1113/JP282058