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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 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 -
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 -
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 -
Investigative Ophthalmology & Visual... Apr 2020Analysis of photoreceptor morphology and gene expression in mispatterned eyes of zebrafish growth differentiation factor 6a (gdf6a) mutants.
PURPOSE
Analysis of photoreceptor morphology and gene expression in mispatterned eyes of zebrafish growth differentiation factor 6a (gdf6a) mutants.
METHODS
Rod and cone photoreceptors were compared between gdf6a mutant and control zebrafish from larval to late adult stages using transgenic labels, immunofluorescence, and confocal microscopy, as well as by transmission electron microscopy. To compare transcriptomes between larval gdf6a mutant and control zebrafish, RNA-Seq was performed on isolated eyes.
RESULTS
Although rod and cone photoreceptors differentiate in gdf6a mutant zebrafish, the cells display aberrant growth and morphology. The cone outer segments, the light-detecting sensory endings, are reduced in size in the mutant larvae and fail to recover to control size at subsequent stages. In contrast, rods form temporarily expanded outer segments. The inner segments, which generate the required energy and proteins for the outer segments, are shortened in both rods and cones at all stages. RNA-Seq analysis provides a set of misregulated genes associated with the observed abnormal photoreceptor morphogenesis.
CONCLUSIONS
GDF6 mutations were previously identified in patients with Leber congenital amaurosis. Here, we reveal a unique photoreceptor phenotype in the gdf6a mutant zebrafish whereby rods and cones undergo abnormal maturation distinct for each cell type. Further, subsequent development shows partial recovery of cell morphology and maintenance of the photoreceptor layer. By conducting a transcriptomic analysis of the gdf6a larval eyes, we identified a collection of genes that are candidate regulators of photoreceptor size and morphology.
Topics: Animals; Fluorescent Antibody Technique; Gene Expression Regulation, Developmental; Growth Differentiation Factor 6; In Situ Hybridization; Larva; Microscopy, Confocal; Microscopy, Electron, Transmission; Morphogenesis; Mutation; Paraffin Embedding; Real-Time Polymerase Chain Reaction; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Zebrafish; Zebrafish Proteins
PubMed: 32293666
DOI: 10.1167/iovs.61.4.9 -
Pflugers Archiv : European Journal of... Sep 2021Rhodopsin is the light receptor in rod photoreceptor cells that initiates scotopic vision. Studies on the light receptor span well over a century, yet questions about... (Review)
Review
Rhodopsin is the light receptor in rod photoreceptor cells that initiates scotopic vision. Studies on the light receptor span well over a century, yet questions about the organization of rhodopsin within the photoreceptor cell membrane still persist and a consensus view on the topic is still elusive. Rhodopsin has been intensely studied for quite some time, and there is a wealth of information to draw from to formulate an organizational picture of the receptor in native membranes. Early experimental evidence in apparent support for a monomeric arrangement of rhodopsin in rod photoreceptor cell membranes is contrasted and reconciled with more recent visual evidence in support of a supramolecular organization of rhodopsin. What is known so far about the determinants of forming a supramolecular structure and possible functional roles for such an organization are also discussed. Many details are still missing on the structural and functional properties of the supramolecular organization of rhodopsin in rod photoreceptor cell membranes. The emerging picture presented here can serve as a springboard towards a more in-depth understanding of the topic.
Topics: Animals; Cell Membrane; Humans; Protein Multimerization; Protein Structure, Secondary; Retinal Rod Photoreceptor Cells; Rhodopsin
PubMed: 33591421
DOI: 10.1007/s00424-021-02522-5 -
Pflugers Archiv : European Journal of... Sep 2021Rod and cone photoreceptors of the vertebrate retina utilize cGMP as the primary intracellular messenger for the visual signaling pathway that converts a light stimulus... (Review)
Review
Rod and cone photoreceptors of the vertebrate retina utilize cGMP as the primary intracellular messenger for the visual signaling pathway that converts a light stimulus into an electrical response. cGMP metabolism in the signal-transducing photoreceptor outer segment reflects the balance of cGMP synthesis (catalyzed by guanylyl cyclase) and degradation (catalyzed by the photoreceptor phosphodiesterase, PDE6). Upon light stimulation, rapid activation of PDE6 by the heterotrimeric G-protein (transducin) triggers a dramatic drop in cGMP levels that lead to cell hyperpolarization. Following cessation of the light stimulus, the lifetime of activated PDE6 is also precisely regulated by additional processes. This review summarizes recent advances in the structural characterization of the rod and cone PDE6 catalytic and regulatory subunits in the context of previous biochemical studies of the enzymological properties and allosteric regulation of PDE6. Emphasis is given to recent advances in understanding the structural and conformational changes underlying the mechanism by which the activated transducin α-subunit binds to-and relieves inhibition of-PDE6 catalysis that is controlled by its intrinsically disordered, inhibitory γ-subunit. The role of the regulator of G-protein signaling 9-1 (RGS9-1) in regulating the lifetime of the transducin-PDE6 is also briefly covered. The therapeutic potential of pharmacological compounds acting as inhibitors or activators targeting PDE6 is discussed in the context of inherited retinal diseases resulting from mutations in rod and cone PDE6 genes as well as other inherited defects that arise from excessive cGMP accumulation in retinal photoreceptor cells.
Topics: Animals; Cyclic Nucleotide Phosphodiesterases, Type 6; Humans; Protein Structure, Secondary; Protein Structure, Tertiary; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Vision, Ocular
PubMed: 33860373
DOI: 10.1007/s00424-021-02562-x -
Pflugers Archiv : European Journal of... Sep 2021Light-evoked voltage responses of rod and cone photoreceptor cells in the vertebrate retina must be converted to a train of synaptic vesicle release events for... (Review)
Review
Light-evoked voltage responses of rod and cone photoreceptor cells in the vertebrate retina must be converted to a train of synaptic vesicle release events for transmission to downstream neurons. This review discusses the processes, proteins, and structures that shape this critical early step in vision, focusing on studies from salamander retina with comparisons to other experimental animals. Many mechanisms are conserved across species. In cones, glutamate release is confined to ribbon release sites although rods are also capable of release at non-ribbon sites. The role of non-ribbon release in rods remains unclear. Release from synaptic ribbons in rods and cones involves at least three vesicle pools: a readily releasable pool (RRP) matching the number of membrane-associated vesicles along the ribbon base, a ribbon reserve pool matching the number of additional vesicles on the ribbon, and an enormous cytoplasmic reserve. Vesicle release increases in parallel with Ca channel activity. While the opening of only a few Ca channels beneath each ribbon can trigger fusion of a single vesicle, sustained release rates in darkness are governed by the rate at which the RRP can be replenished. The number of vacant release sites, their functional status, and the rate of vesicle delivery in turn govern replenishment. Along with an overview of the mechanisms of exocytosis and endocytosis, we consider specific properties of ribbon-associated proteins and pose a number of remaining questions about this first synapse in the visual system.
Topics: Animals; Calcium Channels; Humans; Photic Stimulation; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Synapses; Synaptic Transmission
PubMed: 33779813
DOI: 10.1007/s00424-021-02548-9 -
Annual Review of Vision Science Sep 2018We know a good deal about the operation of the retina when either rod or cone photoreceptors provide the dominant input (i.e., under very dim or very bright conditions).... (Review)
Review
We know a good deal about the operation of the retina when either rod or cone photoreceptors provide the dominant input (i.e., under very dim or very bright conditions). However, we know much less about how the retina operates when rods and cones are coactive (i.e., under intermediate lighting conditions, such as dusk). Such mesopic conditions span 20-30% of the light levels over which vision operates and encompass many situations in which vision is essential (e.g., driving at night). These lighting conditions are challenging because rod and cone signals differ substantially: Rod responses are nearing saturation, while cone responses are weak and noisy. A rich history of perceptual studies guides our investigation of how the retina operates under mesopic conditions and in doing so provides a powerful opportunity to link general issues about parallel processing in neural circuits with computation and perception. We review some of the successes and challenges in understanding the retinal basis of perceptual rod-cone interactions.
Topics: Humans; Mesopic Vision; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod-Cone Interaction; Visual Perception
PubMed: 29883274
DOI: 10.1146/annurev-vision-091517-034055 -
Asia Pacific Journal of Clinical... 2019Docosahexaenoic acid (DHA) is a 22-carbon omega 3 PUFA highly enriched in the neuronal cell membranes and rod outer segment membranes. When DHA is depleted from these... (Review)
Review
Docosahexaenoic acid (DHA) is a 22-carbon omega 3 PUFA highly enriched in the neuronal cell membranes and rod outer segment membranes. When DHA is depleted from these cell membranes it is replaced nearly quantitatively by a 22-carbon omega 6 PUFA, docosapentaenoic acid, which has similar, but less potent, biophysical and physiological properties to DHA. It is speculated that omega 6-docosapentaenoic acid is a buffer to prevent the possible catastrophic effects of DHA depletion on brain and visual function. The primary insult from the loss of DHA from cell membrane glycerophospholipids, and replacement by omega 6-docosapentaenoic acid, is on the flexibility/compression of the membrane lipids which affects the optimal function of integral membrane proteins (receptors, voltage-gated ion channels and enzymes). This leads to effects on second messenger systems, and subsequently affects neurotransmitter concentrations due to 'weakened' signals from the initiating receptors. Remembering there are more than 80 billion neurones and many times more synaptic connections between neurons, a very small loss of "efficiency" in signal due to altered properties of membrane proteins would likely result in meaningful changes in brain and visual function. Additionally, impairment of neurotransmission could be due, in part, to sub-optimal brain energy metabolism (glucose entry into the brain), which is significantly reduced in omega 3 deficiency. Many studies report that dietary omega 3 deficiency results in changes in learning, coping with stress, behavioural changes, and responses in visual function. It is thus concluded that DHA is an essential fatty acid for optimal neuronal function.
Topics: Animals; Brain; Cell Membrane; Docosahexaenoic Acids; Humans; Neurons; Retinal Rod Photoreceptor Cells
PubMed: 31826363
DOI: 10.6133/apjcn.201912_28(4).0002