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The Journal of Cell Biology Sep 2010Humans possess the remarkable ability to perceive color, shape, and motion, and to differentiate between light intensities varied by over nine orders of magnitude.... (Review)
Review
Humans possess the remarkable ability to perceive color, shape, and motion, and to differentiate between light intensities varied by over nine orders of magnitude. Phototransduction--the process in which absorbed photons are converted into electrical responses--is the first stage of visual processing, and occurs in the outer segment, the light-sensing organelle of the photoreceptor cell. Studies of genes linked to human inherited blindness have been crucial to understanding the biogenesis of the outer segment and membrane-trafficking of photoreceptors.
Topics: Animals; Cellular Senescence; Eye; Humans; Morphogenesis; Retinal Rod Photoreceptor Cells; Rhodopsin; Vision, Ocular
PubMed: 20855501
DOI: 10.1083/jcb.201006020 -
Proceedings of the National Academy of... Nov 1996Application of exogenous retinoic acid (RA) to zebrafish during the initial stages of photoreceptor differentiation results in a precocious development of rod...
Application of exogenous retinoic acid (RA) to zebrafish during the initial stages of photoreceptor differentiation results in a precocious development of rod photoreceptors and an inhibition of cone photoreceptor maturation. The acceleration of rod differentiation is observed initially within the ventral retina 3 days after fertilization, following 24 hr of RA application, and within the dorsal retina 4 days after fertilization, following 48 hr of RA application. The differentiation of rods was impeded significantly when the synthesis of endogenous retinoic acid was inhibited by citral prior to the initial stage of rod differentiation. RA-treated embryos labeled for bromodeoxyuridine (BrdU) uptake revealed that RA exerts its effect on a postmitotic cell population within the developing retina. During normal development in zebrafish, rod differentiation is most robust within the ventral retina, a region previously shown to be rich in RA. Our data suggest that the RA signaling pathway is involved in the differentiation and maturation of both the rod and cone photoreceptors within the developing zebrafish retina.
Topics: Animals; Cell Division; Embryo, Nonmammalian; Immunohistochemistry; Photoreceptor Cells; Reference Values; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod Opsins; Transcription, Genetic; Tretinoin; Zebrafish
PubMed: 8917585
DOI: 10.1073/pnas.93.23.13298 -
The Journal of Cell Biology Nov 2015Vision begins in photoreceptor outer segments with light captured by opsins in continually synthesized disc membranes. The process by which rod photoreceptor discs are...
Vision begins in photoreceptor outer segments with light captured by opsins in continually synthesized disc membranes. The process by which rod photoreceptor discs are formed has been controversial. In this issue, Ding et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508093) show conclusively that rod discs are formed by plasma membrane evagination.
Topics: Animals; Cell Membrane; Mammals; Retinal Rod Photoreceptor Cells
PubMed: 26527745
DOI: 10.1083/jcb.201510067 -
The Journal of Comparative Neurology Jun 1997In this study, we have compared spatial and temporal aspects of development of new rods and cones in the adult goldfish by using a combination of bromodeoxyuridine...
In this study, we have compared spatial and temporal aspects of development of new rods and cones in the adult goldfish by using a combination of bromodeoxyuridine immunocytochemistry and opsin in situ hybridization to determine the intervals between terminal mitosis (cell "birth") and expression of opsin mRNA for each photoreceptor cell type. The goldfish opsins include rod opsin and four different cone opsins: red, green, blue, and ultraviolet. In a cohort of photoreceptors born at the same time, rods expressed opsin mRNA within 3 days of cell birth, while expression of cone opsin mRNA required at least 7 days. This temporal discrepancy in differentiation, coupled with a discordance in the site of cell genesis of rods and cones, allowed opsin expression to commence in both cell types in approximately the same retinal location. Commitment to the generic cone phenotype occurred within approximately 6 days throughout the cone cohort, as indicated by expression of interphotoreceptor retinoid-binding protein (IRBP) mRNA, but expression of a specific spectral phenotype was delayed until rods differentiated nearby. Onset of expression of cone opsin mRNA followed a phenotype-specific sequence: red, then green, then blue, and finally ultraviolet; in situ hybridization with two opsin probes confirmed that individual photoreceptors expressed only one type of opsin as they differentiated. This stepwise process of cone differentiation is consistent with the hypothesis that cell-cell interactions among developing photoreceptors may coordinate selection of specific photoreceptor phenotypes.
Topics: Animals; Bromodeoxyuridine; Cell Differentiation; Cell Division; Cellular Senescence; Goldfish; Immunohistochemistry; In Situ Hybridization; RNA, Messenger; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod Opsins; Time Factors
PubMed: 9183694
DOI: 10.1002/(sici)1096-9861(19970602)382:2<272::aid-cne10>3.0.co;2-u -
Cellular and Molecular Life Sciences :... Feb 2000Photoreceptors are the most abundant cell type in the vertebrate neural retina. Like the other retinal neurons and the Müller glia, they arise from a population of... (Review)
Review
Photoreceptors are the most abundant cell type in the vertebrate neural retina. Like the other retinal neurons and the Müller glia, they arise from a population of precursor cells that are multipotent and intrinsic to the retina. Approximately 10 years ago, several studies demonstrated that retinal precursor cells (RPCs) are competent to respond to environmental factors that promote cell type determination and differentiation. Since those studies, significant effort has been directed at identifying the molecular nature of these environmental signals and understanding the precise mechanisms they employ to drive RPCs towards the different retinal fates. In this review, we describe the recent progress toward understanding how environmental factors influence the development of vertebrate rod photoreceptors.
Topics: Animals; Biological Factors; Cell Differentiation; Growth Substances; Hedgehog Proteins; Laminin; Proteins; Retinal Rod Photoreceptor Cells; Solubility; Stem Cells; Taurine; Trans-Activators; Tretinoin
PubMed: 10766019
DOI: 10.1007/PL00000686 -
Cell Death and Differentiation Jul 2010Rod-derived cone viability factor (RdCVF) is a thioredoxin-like protein, which has therapeutic potential for rod-cone dystrophies such as retinitis pigmentosa (RP). Cone...
Rod-derived cone viability factor (RdCVF) is a thioredoxin-like protein, which has therapeutic potential for rod-cone dystrophies such as retinitis pigmentosa (RP). Cone loss in rodent models of RP is effectively reduced by RdCVF treatment. In this study, we investigate the physiological role of RdCVF in the retina by analyzing the phenotype of the mouse lacking the RdCVF gene, Nxnl1. Although the mice do not show an obvious developmental defect, an age-related reduction of both cone and rod function and a delay in the dark-adaptation of the retina are recorded by electroretinogram (ERG). This functional change is accompanied by a 17% reduction in cone density and a 20% reduction in thickness of the outer nuclear layer. The transcriptome of the retina reveals early changes in the expression of genes involved in programmed cell death, stress-response and redox-signaling, which is followed by a generalized injury response with increased microglial activation, GFAP, FGF2 and lipid peroxidation levels. Furthermore, cones of the mice lacking Nxnl1 are more sensitive to oxidative stress with a reduction of 65% in the cone flicker ERG amplitude measured under hyperoxic conditions. We show here that the RdCVF gene, in addition to therapeutic properties, has an essential role in photoreceptor maintenance and resistance to retinal oxidative stress.
Topics: Animals; Apoptosis; Eye Proteins; Fibroblast Growth Factor 2; Gene Expression Profiling; Lipid Peroxidation; Mice; Mice, Knockout; Oxidative Stress; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Signal Transduction; Thioredoxins
PubMed: 20139892
DOI: 10.1038/cdd.2010.2 -
PloS One 2018Retinitis pigmentosa (RP), an inherited retinal degenerative disease, is characterized by a progressive loss of rod photoreceptors followed by loss of cone...
Retinitis pigmentosa (RP), an inherited retinal degenerative disease, is characterized by a progressive loss of rod photoreceptors followed by loss of cone photoreceptors. Previously, when tissue inhibitor of metalloproteinase 1 (TIMP1), a key extracellular matrix (ECM) regulator that binds to and inhibits activation of Matrix metallopeptidase 9 (MMP9) was intravitreal injected into eyes of a transgenic rhodopsin rat model of RP, S334ter-line3, we discovered cone outer segments are partially protected. In parallel, we reported that a specific MMP9 and MMP2 inhibitor, SB-3CT, interferes with mechanisms leading to rod photoreceptor cell death in an MMP9 dependent manner. Here, we extend our initial rat studies to examine the potential of TIMP1 as a treatment in retinal degeneration by investigating neuroprotective effects in a classic mouse retinal degeneration model, rdPde6b-/- (rd1). The results clearly demonstrate that intravitreal injections of TIMP1 produce extended protection to delay rod photoreceptor cell death. The mean total number of rods in whole-mount retinas was significantly greater in TIMP-treated rd1 retinas (postnatal (P) 30, P35 (P<0.0001) and P45 (P<0.05) than in saline-treated rd1 retinas. In contrast, SB-3CT did not delay rod cell death, leading us to further investigate alternative pathways that do not involve MMPs. In addition to inducing phosphorylated ERK1/2, TIMP1 significantly reduces BAX activity and delays attenuation of the outer nuclear layer (ONL). Physiological responses using scotopic electroretinograms (ERG) reveal b-wave amplitudes from TIMP1-treated retinas are significantly greater than from saline-treated rd1 retinas (P<0.05). In later degenerative stages of rd1 retinas, photopic b-wave amplitudes from TIMP1-treated rd1 retinas are significantly larger than from saline-treated rd1 retinas (P<0.05). Our findings demonstrate that TIMP1 delays photoreceptor cell death. Furthermore, this study provides new insights into how TIMP1 works in the mouse animal model of RP.
Topics: Animals; Cell Death; Extracellular Signal-Regulated MAP Kinases; Female; Heterocyclic Compounds, 1-Ring; Male; Matrix Metalloproteinase Inhibitors; Mice, Inbred C57BL; Mice, Transgenic; Neuroprotective Agents; Nuclear Proteins; RNA-Binding Proteins; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa; Sulfones; Tissue Inhibitor of Metalloproteinase-1; bcl-2-Associated X Protein
PubMed: 29742163
DOI: 10.1371/journal.pone.0197322 -
Brain Research Oct 2014The aim of this study was to investigate rod and cone photoreceptor degeneration in organotypic cultures of adult porcine retina. Our hypothesis was that the...
The aim of this study was to investigate rod and cone photoreceptor degeneration in organotypic cultures of adult porcine retina. Our hypothesis was that the photoreceptors accumulate opsins, which, together with exposure to cyclic dim light illumination, induce autophagy and endoplasmic reticulum stress (ER-stress) to overcome damaging protein overload. For this purpose, retinas were cultured for 48 h and 72 h during which they were illuminated with dim light for 8h/day; specimens were analyzed by means of immunohistochemistry, Western blot, real-time polymerase chain reaction (PCR) and transmission electron microscopy. ER-stress and photoreceptor degeneration was observed in conventionally cultured retinas. The additional stress in the form of dim light illumination for 8h/day resulted in increased levels of the ER-stress markers GRP78/BiP and CHOP, as well as increased level of active caspase-12. Increased autophagic processes in cone and rod photoreceptors were detected by LC3B-II increases and occurrence of autophagosomes at the ultrastructural level. Illumination also resulted in altered protein expression for autophagy inducers such as p62 and Beclin-1. Moreover, there was a decrease in phosphorylated mammalian target of rapamycin (mTOR), which further indicate an increase of autophagy. Rod and cone photoreceptors in retinas from a diurnal animal that were exposed to dim light illumination in vitro displayed autophagy and ER-stress processes. As no alteration of rhodopsin mRNA was observed, autophagy and ER-stress are suggested to decrease rhodopsin protein at the posttranscriptional level.
Topics: Animals; Autophagy; Circadian Rhythm; Endoplasmic Reticulum Stress; Organ Culture Techniques; Photic Stimulation; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rhodopsin; Swine; Synapses
PubMed: 25173074
DOI: 10.1016/j.brainres.2014.08.055 -
Investigative Ophthalmology & Visual... Dec 2015Ambient light is both a stimulus for visual function and a regulator of photoreceptor physiology. However, it is not known if light can regulate any aspect of...
PURPOSE
Ambient light is both a stimulus for visual function and a regulator of photoreceptor physiology. However, it is not known if light can regulate any aspect of photoreceptor development. The purpose of this study was to investigate whether ambient light is required for the development of mouse rod photoreceptors.
METHODS
Newborn mouse pups (C57BL/6) were reared in either cyclic light (LD) or constant dark (DD). Pups were collected at postnatal day (P)5, P10, P17, or P24. We performed retinal morphometric and cell death analysis at P5, P10, and P17. Rhodopsin expression was assessed using immunofluorescence, Western blot, and quantitative RT-PCR analysis. Electroretinograms were performed at P17 and P24. Radioimmunoassay and ELISA were used to follow changes in thyroid hormone levels in the serum and vitreous.
RESULTS
In the DD pups, the outer nuclear layer was significantly thinner at P10 and there were higher numbers of apoptotic cells at P5 compared to the LD pups. Rhodopsin expression was lower at P10 and P17 in DD pups. Electroretinogram a-waves were reduced in amplitude at P17 in the DD pups. The DD animals had lower levels of circulating thyroid hormones at P10. Light-mediated changes in thyroid hormones occur as early as P5, as we detected lower levels of total triiodothyronine in the vitreous from the DD animals. Drug-induced developmental hypothyroidism resulted in lower rhodopsin expression at P10.
CONCLUSIONS
Our data demonstrate that light exposure during postnatal development is required for rod photoreceptor development and that this effect could be mediated by thyroid hormone signaling.
Topics: Animals; Animals, Newborn; Blotting, Western; Cell Death; DNA; Dark Adaptation; Disease Models, Animal; Electroretinography; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Developmental; Light; Light Signal Transduction; Mice; Mice, Inbred C57BL; Retinal Degeneration; Retinal Rod Photoreceptor Cells; Reverse Transcriptase Polymerase Chain Reaction; Rhodopsin; Thyroid Hormones
PubMed: 26720479
DOI: 10.1167/iovs.15-17743 -
Proceedings of the National Academy of... Dec 2015The vertebrate photoreceptor cell contains an elaborate cilium that includes a stack of phototransductive membrane disks. The disk membranes are continually renewed, but...
The vertebrate photoreceptor cell contains an elaborate cilium that includes a stack of phototransductive membrane disks. The disk membranes are continually renewed, but how new disks are formed remains poorly understood. Here we used electron microscope tomography to obtain 3D visualization of the nascent disks of rod photoreceptors in three mammalian species, to gain insight into the process of disk morphogenesis. We observed that nascent disks are invariably continuous with the ciliary plasma membrane, although, owing to partial enclosure, they can appear to be internal in 2D profiles. Tomographic analyses of the basal-most region of the outer segment show changes in shape of the ciliary plasma membrane indicating an invagination, which is likely a first step in disk formation. The invagination flattens to create the proximal surface of an evaginating lamella, as well as membrane protrusions that extend between adjacent lamellae, thereby initiating a disk rim. Immediately distal to this initiation site, lamellae of increasing diameter are evident, indicating growth outward from the cilium. In agreement with a previous model, our data indicate that mature disks are formed once lamellae reach full diameter, and the growth of a rim encloses the space between adjacent surfaces of two lamellae. This study provides 3D data of nascent and mature rod photoreceptor disk membranes at unprecedented z-axis depth and resolution, and provides a basis for addressing fundamental questions, ranging from protein sorting in the photoreceptor cilium to photoreceptor electrophysiology.
Topics: Animals; Cats; Cilia; Intracellular Membranes; Macaca mulatta; Mice; Retinal Rod Photoreceptor Cells
PubMed: 26578801
DOI: 10.1073/pnas.1516309112