A searchlight through the fog.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Retinal Rod Photoreceptor Cells”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase.
Retinitis pigmentosa (RP) constitutes a group of genetically heterogeneous progressive photoreceptor degenerations leading to blindness and affecting 50,000-100,000 people in the U.S. alone. Over 20 different RP loci have been mapped, of which six have been identified. Three of these encode members of the rod photoreceptor visual transduction cascade: rhodopsin, the rod cGMP-gated cation channel alpha subunit, and the beta subunit of cGMP-phosphodiesterase (PDEB). As null mutations in PDEB cause some cases of RP and since both alpha and beta subunits are required for full phosphodiesterase activity, we examined the gene encoding the alpha subunit of cGMP phosphodiesterase (PDEA) in 340 unrelated patients with RP. We found three point mutations in PDEA in affected members of two pedigrees with recessive RP. Each mutation alters an essential functional domain of the encoded protein and likely disrupts its catalytic function. PDEA is the seventh RP gene identified, highlighting the extensive genetic heterogeneity of the disorder and encouraging further investigation into the role of other members of the phototransduction cascade in RP.
3',5'-Cyclic-GMP Phosphodiesterases↗
Support for the equivalent light hypothesis for RP.
Explore the source record for details and available documents.
Animals↗
For whales and seals the ocean is not blue: a visual pigment loss in marine mammals.
Most terrestrial mammals have colour vision based on two spectrally different visual pigments located in two types of retinal cone photoreceptors, i.e. they are cone dichromats with long-to-middle-wave-sensitive (commonly green) L-cones and short-wave-sensitive (commonly blue) S-cones. With visual pigment-specific antibodies, we here demonstrate an absence of S-cones in the retinae of all whales and seals studied. The sample includes seven species of toothed whales (Odontoceti) and five species of marine carnivores (eared and earless seals). These marine mammals have only L-cones (cone monochromacy) and hence are essentially colour-blind. For comparison, the study also includes the wolf, ferret and European river otter (Carnivora) as well as the mouflon and pygmy hippopotamus (Artiodactyla), close terrestrial relatives of the seals and whales, respectively. These have a normal complement of S-cones and L-cones. The S-cone loss in marine species from two distant mammalian orders strongly argues for convergent evolution and an adaptive advantage of that trait in the marine visual environment. To us this suggests that the S-cones may have been lost in all whales and seals. However, as the spectral composition of light in clear ocean waters is increasingly blue-shifted with depth, an S-cone loss would seem particularly disadvantageous. We discuss some hypotheses to explain this paradox.
Animals↗
Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa.
Mutations in the gene encoding the beta subunit of rod cGMP phosphodiesterase are known causes of photoreceptor degeneration in two animal models of retinitis pigmentosa, the rd (retinal degeneration) mouse and the Irish setter dog with rod/cone dysplasia. Here we report a screen of 92 unrelated patients with autosomal recessive retinitis pigmentosa for defects in the human homologue of this gene. We identified seven different mutations that cosegregate with the disease. They were found among four patients with each patient heterozygously carrying two mutations. All of these mutations are predicted to affect the putative catalytic domain, probably leading to a decrease in phosphodiesterase activity and an increase in cGMP levels within rod photoreceptors. Mutations in the gene encoding the beta subunit of rod phosphodiesterase are the most common identified cause of autosomal recessive retinitis pigmentosa, accounting for approximately 4% of cases in North America.
3',5'-Cyclic-GMP Phosphodiesterases↗
Retinitis pigmentosa: unfolding its mystery.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Cell fate determination in the vertebrate retina.
In the vertebrate central nervous system, the retina has been a useful model for studies of cell fate determination. Recent results from studies conducted in vitro and in vivo suggest a model of retinal development in which both the progenitor cells and the environment change over time. The model is based upon the notion that the mitotic cells within the retina change in their response properties, or "competence", during development. These changes presage the ordered appearance of distinct cell types during development and appear to be necessary for the production of the distinct cell types. As the response properties of the cells change, so too do the environmental signals that the cells encounter. Together, intrinsic properties and extrinsic cues direct the choice of cell fate.
Animals↗
Regulation of the kinetics of phosducin phosphorylation in retinal rods.
Phosducin (Pd) is a widely expressed phosphoprotein that regulates G-protein (G) signaling. Unphosphorylated Pd binds to Gbetagamma subunits and blocks their interaction with Galpha. This binding sequesters Gbetagamma and inhibits both receptor-mediated activation of Galpha and direct interactions between Gbetagamma and effector enzymes. When phosphorylated by cAMP-dependent protein kinase, Pd does not affect these functions of Gbetagamma. To further understand the role of Pd in regulating G-protein signaling in retinal rod photoreceptor cells, we have measured the abundance of Pd in rods and examined factors that control the rate of Pd phosphorylation. Pd is expressed at a copy number comparable to that for the rod G-protein, transducin (Gt). The ratio of rhodopsin (Rho) to Pd is 15. 5 +/- 3.5 to 1. The rate of Pd phosphorylation in rod outer segment preparations was dependent on [cAMP]. K1/2 for cAMP was 0.56 +/- 0. 09 microM, and the maximal rate of phosphorylation was approximately 500 pmol PO4 incorporated/min/nmol Rho. In the presence of Gtbetagamma this rate was decreased approximately 50-fold. From these data, one can estimate a t1/2 of approximately 3 min for the rephosphorylation of Pd in rods during the recovery period after a light response. This relatively slow rephosphorylation of the Pd.Gtbetagamma complex may provide a period of molecular memory in which sensitivity to further light stimuli is reduced as a result of sequestration of Gtbetagamma by Pd.
Adaptation, Physiological↗
A novel homozygous Ile535Asn mutation in the rod cGMP phosphodiesterase beta-subunit gene in two brothers of a Japanese family with autosomal recessive retinitis pigmentosa.
PURPOSE: Recently, mutations in several genes have been identified as being responsible for the pathogenesis of autosomal recessive retinitis pigmentosa (arRP). These genes include rhodopsin, beta-subunit of rod cGMP phosphodiesterase (PDEB), alpha-subunit of rod cGMP phosphodiesterase (PDEA), and alpha-subunit of rod cGMP-gated channel. We here attempted to identify a novel mutation in the PDEB gene in Japanese arRP patients. METHODS: Using the PCR-SSCP method, sequencing analysis, and restriction endonuclease digestion assay, we analyzed the PDEB gene in 17 Japanese families with non-dominant retinitis pigmentosa. RESULTS: A novel Ile535Asn mutation was identified in two patients in a single family and the mutation cosegregated with RP in this family. Among 90 unrelated healthy individuals, no one was identified as homozygous for this mutation, except for one individual who was found to be heterozygous. CONCLUSIONS: Isoleucine at codon 535 in the PDEB gene is conserved among various mammals. Missense mutations of the PDEB gene causing arRP have been reported in a limited region (codon 527-codon 699) in which codon 535 is located. Thus, the Ile535Asn mutation is an additional missense mutation which is responsible for the pathogenesis of arRP.
3',5'-Cyclic-GMP Phosphodiesterases↗
Clinical phenotype in a Swedish family with a mutation in the IMPDH1 gene.
PURPOSE: Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) have recently been discovered to cause a form of autosomal dominant retinitis pigmentosa (adRP). Such mutations are estimated to account for approximately 2-5% of the adRP cases among Americans of European origin and Europeans. Aiming towards an understanding of the molecular background of retinitis pigmentosa, this paper describes the phenotype of a Swedish family with a mutation in IMPDH1. METHODS: Venous blood samples were obtained from 12 family members and screened for mutations in IMPDH1. Six individuals with the mutation were examined clinically and with full-field electroretinography (ERG), dark adaptometry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). Also reviewed were the clinical findings and ERGs obtained 14 years earlier. RESULTS: The proband and eight other relatives from three generations were found to harbor the Asp226Asn mutation in IMPDH1. These individuals, from three generations, showed clinical and electrophysiological signs of retinitis pigmentosa. The cone responses to the full-field, 30-Hz flicker ERG demonstrated an unusual pattern, with implicit times within normal limits or only slightly prolonged. Rod ERG responses, however, were undetectable. OCT showed intraretinal fluid and swelling, changes that were more pronounced in younger individuals. mfERG showed residual preserved central function. The older the individual, the smaller the area of preserved central function. CONCLUSION: In this family with a mutation in IMPDH1, we found a specific phenotype with rod function affected more than cone function, foveal edema, and central retinal function preserved for a long period of time. Foveal edema could be a pathogenic feature in this form of retinal degeneration.
Adolescent↗
New aspects of an old theme: the genetic basis of human color vision.
Explore the source record for details and available documents.
Color Perception↗
On the genetics of retinitis pigmentosa and on mutation-independent approaches to therapeutic intervention.
Retinitis pigmentosa (RP), the group of hereditary conditions involving death of retinal photoreceptors, represents the most prevalent cause of visual handicap among working populations in developed countries. Here we provide an overview of the molecular pathologies associated with such disorders, from which it becomes clearly apparent that RP is one of the most genetically heterogeneous of hereditary conditions for which molecular pathologies have so far been elucidated. While heterogeneity of such magnitude would appear to represent a major impediment to the development of therapeutics, mutation-independent approaches to therapy are being developed to effectively by-pass such diversity in genetic aetiology. The implications of such technologies in terms of therapeutic intervention in RP, and indeed other genetically heterogeneous conditions, will be addressed.
3' Untranslated Regions↗
ABCA4 mutations causing mislocalization are found frequently in patients with severe retinal dystrophies.
ABCA4, also called ABCR, is a retinal-specific member of the ATP-binding cassette (ABC) family that functions in photoreceptor outer segments as a flipase of all-trans retinal. Homozygous and compound heterozygous ABCA4 mutations are associated with various autosomal recessive retinal dystrophies, whereas heterozygous ABCA4 mutations have been associated with dominant susceptibility to age-related macular degeneration in both humans and mice. We analyzed a cohort of 29 arRP families for the mutations in ABCA4 with a commercial microarray, ABCR-400 in addition to direct sequencing and segregation analysis, and identified both mutant alleles in two families (7%): compound heterozygosity for missense (R602W) and nonsense (R408X) alleles and homozygosity for a complex [L541P; A1038V] allele. The missense mutations were analyzed functionally in the photoreceptors of Xenopus laevis tadpoles, which revealed mislocalization of ABCA4 protein. These mutations cause retention of ABCA4 in the photoreceptor inner segment, likely by impairing correct folding, resulting in the total absence of physiologic protein function. Patients with different retinal dystrophies harboring two misfolding alleles exhibit early age-of-onset (AO) (5-12 years) of retinal disease. Our data suggest that a class of ABCA4 mutants may be an important determinant of the AO of disease.
ATP-Binding Cassette Transporters↗
Localization of gamma-aminobutyric acid (GABA) receptor rho 3 subunit in rat retina.
We used digoxigenin-labelled single strand DNA probes to examine the expression of the mRNA encoding gamma-aminobutyric acid receptor rho 3 subunit in sections of the adult rat retina. Transcript for the rho 3 subunit was found in cell somata of a portion of cells lying in the ganglion cell layer.
Animals↗
The origins of colour vision in vertebrates.
The capacity for colour vision is mediated by the comparison of the signal intensities from photoreceptors of two or more types that differ in spectral sensitivity. Morphological, physiological and molecular analyses of the retina in an agnathan (jawless) fish, the lamprey Geotria australis, may hold important clues to the origins of colour vision in vertebrates. Lampreys are extant representatives of an ancient group of vertebrates, the origins of which are thought to date back to at least the early Cambrian, approximately 540 million years ago. G. australis possesses five photoreceptor types, each with cone-like ultrastructural features and different spectral sensitivities. Recent molecular genetic studies have also revealed that five visual pigment (opsin) genes are expressed in the retina, each of which is orthologous to the major classes of vertebrate opsin genes. These findings reveal that multiple opsin genes originated very early in vertebrate evolution, prior to the separation of the jawed and jawless vertebrate lineages, thereby providing the genetic basis for colour vision in all vertebrates.
Animals↗
Differences in adaptation between on- and off-centre ganglion cells and rod-mediated cone sensitization in cat retina.
1. Response properties of on- and off-centre retinal ganglion cells were investigated in cats. The stimulus parameters were selected so as to demonstrate interactions between the rod and the cone systems. 2. Response versus log stimulus intensity (R-log I) functions were determined for the receptive field centres while both test stimulus irradiance and the background illumination were varied over a range up to 7 log units. In order to determine the course of adaptation to chromatic stimuli, threshold versus intensity (t.v.i.) functions were measured over a wide range of adaptation levels. 3. An increase in background illuminance produced a shift of the R-log I functions to higher irradiances of test stimuli in most ganglion cells, indicating a desensitization of the centre response in the presence of background lights. Using test stimuli which most efficiently stimulate the rods (501 nm), clear differences could be seen in the adaptation behaviour of on- and off-centre ganglion cells. Chromatic backgrounds (blue-green and orange) reduced the responses of off-centre cells more than those of on-centre cells (the difference between them amounting to as much as 2 log units). Simultaneously, equivalent t.v.i. functions had significantly steeper slopes (0.94 and 1.1) in the linear proportions of off-centre cells compared to on-centre cells (0.76 and 0.75) under light levels mediated by rods. Such differences were not observed when a test stimulus of 575 nm was used which resulted primarily in stimulating the long-wavelength cone (L-cone) system. 4. In a subpopulation of off-centre cells (20% of the total number of off-centre cells recorded), a strikingly different adaptation behaviour was observed. Here, the presentation of a dim short-wavelength background produced a shift of R-log I functions to lower test stimulus irradiances. The receptive field centre became even more sensitive, by up to 1.5 log units, in the presence of dim adapting backgrounds rather than in the dark-adapted state. Accordingly, the t.v.i. function did not increase monotonically but showed a 'dip' in the presence of dim backgrounds. Only at photoic levels, the t.v.i. functions revealed a response behaviour similar to the other ganglion cells. The sensitization with dim backgrounds was only observed in the case of test stimuli designed to stimulate the cone system (575 nm) and in the presence of a rod-adapting blue-green background.(ABSTRACT TRUNCATED AT 400 WORDS)
Adaptation, Physiological↗