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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 -
Advances in Experimental Medicine and... 2019Retinal degeneration includes a variety of diseases for which there is no regenerative therapy. Cellular transplantation is one potential approach for future therapy for... (Review)
Review
Retinal degeneration includes a variety of diseases for which there is no regenerative therapy. Cellular transplantation is one potential approach for future therapy for retinal degeneration, and stem cells have emerged as a promising source for future cell therapeutics. One major barrier to therapy is the ability to specify individual photoreceptor lineages from a variety of stem cell sources. In this review, we focus on photoreceptor genesis from progenitor populations in the developing embryo and how this understanding has given us the tools to manipulate cultures to specific unique rod and cone lineages from adult stem cell populations. We discuss experiments and evidence uncovering the lineage mechanisms at play in the establishment of fate-specific rod and cone photoreceptor progenitors. This may lead to an improved understanding of retinal development in vivo, as well as new cell sources for transplantation.
Topics: Cell Differentiation; Humans; Retina; Retinal Cone Photoreceptor Cells; Retinal Degeneration; Retinal Rod Photoreceptor Cells; Stem Cells
PubMed: 31884669
DOI: 10.1007/978-3-030-27378-1_90 -
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 -
Progress in Retinal and Eye Research Nov 2011The retinas of postembryonic teleost fish continue to grow for the lifetime of the fish. New retinal cells are added continuously at the retinal margin, by stem cells... (Review)
Review
The retinas of postembryonic teleost fish continue to grow for the lifetime of the fish. New retinal cells are added continuously at the retinal margin, by stem cells residing at the circumferential germinal zone. Some of these retinal cells differentiate as Müller glia with cell bodies that reside within the inner nuclear layer. These glia retain some stem cell properties in that they carry out asymmetric cell divisions and continuously generate a population of transit-amplifying cells--the rod photoreceptor lineage--that are committed to rod photoreceptor neurogenesis. These rod progenitors progress through a stereotyped sequence of changes in gene expression as they continue to divide and migrate to the outer nuclear layer. Now referred to as rod precursors, they undergo terminal mitoses and then differentiate as rods, which are inserted into the existing array of rod and cone photoreceptors. The rod lineage displays developmental plasticity, as rod precursors can respond to the loss of rods through increased proliferation, resulting in rod replacement. The stem cells of the rod lineage, Müller glia, respond to acute damage of other retinal cell types by increasing their rate of proliferation. In addition, the Müller glia in an acutely damaged retina dedifferentiate and become multipotent, generating new, functional neurons. This review focuses on the cells of the rod lineage and includes discussions of experiments over the last 30 years that led to their identification and characterization, and the discovery of the stem cells residing at the apex of the lineage. The plasticity of cells of the rod lineage, their relationships to cone progenitors, and the applications of this information for developing future treatments for human retinal disorders will also be discussed.
Topics: Animals; Cell Lineage; Neurogenesis; Neuronal Plasticity; Retina; Retinal Rod Photoreceptor Cells; Stem Cells; Transcription Factors; Zebrafish
PubMed: 21742053
DOI: 10.1016/j.preteyeres.2011.06.004 -
Physiology & Behavior Oct 2005The zebrafish has rapidly become a favored model vertebrate organism, well suited for studies of developmental processes using large-scale genetic screens. In... (Review)
Review
The zebrafish has rapidly become a favored model vertebrate organism, well suited for studies of developmental processes using large-scale genetic screens. In particular, zebrafish morphological and behavioral genetic screens have led to the identification of genes important for development of the retinal photoreceptors. This may help clarify the genetic mechanisms underlying human photoreceptor development and dysfunction in retinal diseases. In this review, we present the advantages of zebrafish as a vertebrate model organism, summarize retinal and photoreceptor cell development in zebrafish, with emphasis on the rod photoreceptors, and describe zebrafish visual behaviors that can be used for genetic screens. We then describe some of the photoreceptor cell mutants that have been isolated in morphological and behavioral screens and discuss the limitations of current screening methods for uncovering mutations that specifically affect rod function. Finally, we present some alternative strategies to target the rod developmental pathway in zebrafish.
Topics: Animals; Animals, Genetically Modified; Behavior, Animal; Models, Animal; Retinal Rod Photoreceptor Cells; Zebrafish
PubMed: 16199068
DOI: 10.1016/j.physbeh.2005.08.020 -
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 -
Current Biology : CB Mar 2019Retinal dopamine is released by a specialized subset of amacrine cells in response to light and has a potent influence on how the retina responds to, and encodes, visual...
Retinal dopamine is released by a specialized subset of amacrine cells in response to light and has a potent influence on how the retina responds to, and encodes, visual information. Here, we address the critical question of which retinal photoreceptor is responsible for coordinating the release of this neuromodulator. Although all three photoreceptor classes-rods, cones, and melanopsin-containing retinal ganglion cells (mRGCs)-have been shown to provide electrophysiological inputs to dopaminergic amacrine cells (DACs), we show here that the release of dopamine is defined only by rod photoreceptors. Remarkably, this rod signal coordinates both a suppressive signal at low intensities and drives dopamine release at very bright light intensities. These data further reveal that dopamine release does not necessarily correlate with electrophysiological activity of DACs and add to a growing body of evidence that rods define aspects of retinal function at very bright light levels.
Topics: Amacrine Cells; Animals; Dopamine; Female; Male; Mice; Retinal Rod Photoreceptor Cells
PubMed: 30799247
DOI: 10.1016/j.cub.2019.01.042 -
Biotechnology Advances 2014Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the... (Review)
Review
Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application.
Topics: Animals; Cell Transplantation; Embryonic Stem Cells; Haplorhini; Humans; Mice; Retina; Retinal Degeneration; Retinal Rod Photoreceptor Cells
PubMed: 24412415
DOI: 10.1016/j.biotechadv.2014.01.001 -
Comptes Rendus Biologies Feb 2005Neuroprotection of photoreceptor cells in rod-cone dystrophies: from cell therapy to cell signalling. Neuroprotection of photoreceptor cells in rod-cone degenerations is... (Review)
Review
Neuroprotection of photoreceptor cells in rod-cone dystrophies: from cell therapy to cell signalling. Neuroprotection of photoreceptor cells in rod-cone degenerations is primarily targeted at preventing the loss of function. Strategies for protecting rod cells should therefore aim not only at structural preservation but also must be assessed using functional parameters (e.g., electroretinogram). Given the number of mutations leading to an impaired visual response of rods, the preservation of cones is a realistic approach since (1) numerous mutations do not affect proteins expressed by cones; (2) the secondary degeneration of cones is the main event leading to profound visual impairment; (3) even a small proportion of functional cones is sufficient for major visual functions. Our group has (1) established and confirmed the existence of non cell autonomous mechanisms promoting cone cell viability; (2) shown that rod cell protection or replacement provides a mean to extend the survival of cones; (3) demonstrated that rod-cone trophic interactions are mediated by diffusible proteins; (4) identified by expression cloning a protein mediating such interactions: RdCVF (Rod-derived Cone Viability Factor). These studies provide clues for broad neuroprotective therapies of rod-cone dystrophies.
Topics: Animals; Humans; Photoreceptor Cells, Vertebrate; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Signal Transduction; Vision, Ocular
PubMed: 15771002
DOI: 10.1016/j.crvi.2004.12.007 -
Progress in Brain Research 2001
Review
Topics: Animals; Humans; Retina; Retinal Cone Photoreceptor Cells; Retinal Degeneration; Retinal Diseases; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa
PubMed: 11420978
DOI: 10.1016/s0079-6123(01)31051-8