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PubMed1997

Early emergence of photoreceptor mosaicism in the primate retina revealed by a novel cone-specific monoclonal antibody.

We have examined the emergence of the photoreceptor mosaic in fetal macaque monkeys by using a novel monoclonal antibody, 7G6, that recognizes all cones in the adult primate retina. In the fetal retina, however, between embryonic (E) day 80 and E130, some opsin-positive cones were not labeled by 7G6. Double-labeling experiments revealed that though long and middle wavelength-sensitive fetal cones are 7G6-positive, a subset of short wavelength-sensitive cones are delayed in their acquisition of 7G6 immunoreactivity. Heterogeneity in cone labeling with 7G6 was evident at all fetal ages. The onset of 7G6 immunoreactivity, surprisingly, precedes both the expression of the cone opsins and the formation of synaptic contacts in the outer plexiform layer. Specifically, a population of cones was labeled in the periphery of the E65 retina, concomitant with ongoing cone genesis. Moreover, early-differentiating 7G6-positive cones are organized into a regular array in immature, peripheral regions of the fetal retina indicating that the spatial arrangement of cones is initiated either during active cone proliferation or the initial differentiation of these cells. These results suggest that the periodic spacing of cones in the primate retina emerges autonomously within the photoreceptor layer, prior to the formation of synaptic connections within the retina or with the brain.

Animals↗
PubMed1997

Role of the pineal organ in the photoregulated hatching of the Atlantic halibut.

The timing of hatching in the Atlantic halibut (Hippoglossus hippoglossus) has been suggested to be regulated by environmental light conditions. However, the photosensory organ that perceives the triggering light has not been identified. In the present study, we investigated the morphogenesis of the pineal organ and the neurochemical differentiation of photoreceptors in the pineal organ and the retina of the Atlantic halibut during embryonic development. Immunocytochemical techniques were used for detection of integral protein components of the phototransduction process: opsins, arrestin (S-antigen) and alpha-transducin. We also studied the expression of serotonin (5-HT), a precursor of the neurohormone melatonin known to be synthesized by pineal photoreceptors. In the pineal anlage, opsin immunoreactive (ir) cells appear at 11 days post-fertilization (pf), arrestin, alpha-transducin and serotonin ir cells appear at 14 days pf; hatching took place 15 days pf. The retina contained no immunoreactive cells in embryos or in newly hatched larva. During this period, the pineal anlage is morphologically discernible only as a wedge-shaped region in the diencephalic roof, where elongated cells are aligned with their long axes converging toward a centrally located presumptive pineal lumen. The results show that the pineal photoreceptors contain serotonin and molecules involved in the phototransduction cascade before hatching. We suggest that the pineal organ has the capacity to perceive and mediate photic information before hatching in halibut embryos, and may thereby influence the timing of hatching.

Animals↗
PubMed1998

Ribozyme-targeted destruction of RNA associated with autosomal-dominant retinitis pigmentosa.

PURPOSE: To design ribozymes--catalytic RNA molecules--to cleave the P23H and S334Ter mutant mRNA selectively and to test them in vitro to determine their potential as therapeutic agents in the prevention of autosomal dominant retinitis pigmentosa. METHODS: Synthetic RNA targets were used in cleavage assays to determine the catalytic efficiencies of the ribozymes in vitro. Cleavage products were analyzed by denaturing polyacrylamide gel electrophoresis. Total retinal RNA was also used as a substrate, and opsin mRNA cleavage was assayed by reverse transcription-polymerase chain reaction. RESULTS: All three ribozymes cleaved the mutant target specifically. Substrate cleavage was seen in less than 5 mM magnesium and was detectable after 15 minutes of incubation. The most active ribozyme against the P23H target was the hammerhead (kcat:K(m) [Michaelis-Menton constant] ratio = 5 x 10(7) M/min), then the P23H hairpin ribozyme (kcat:K(m) ratio = 9 x 10(5) M/min) and the S334Ter hammerhead (kcat:K(m) ratio = 8 x 10(5) M/min). No cleavage activity was observed, when wild-type target sequences or inactive control ribozymes were used. The ribozymes bound and specifically digested the intact mutant opsin mRNA in the presence of all normal retinal RNA. CONCLUSIONS: Ribozymes can discriminate between the mutant and wild-type sequences of mRNA associated with autosomal dominant retinitis pigmentosa. The kinetics and specificity of ribozyme cleavage indicate that they should reduce the amount of aberrant rhodopsin in the rod cells and may have potential as therapeutic agents against genetic disease.

Animals↗
PubMed1998

Sequential genesis and determination of cone and rod photoreceptors in Xenopus.

In this study, we addressed the temporal sequence of photoreceptor fate determination in Xenopus laevis by examining a number of key events during early cone and rod development. We compared the relative timing and spatial pattern of cone and rod specification using a number of cell type-specific markers, including probes to a long wavelength-sensitive opsin which is expressed by the major cone subtype. Our results show that cones are initially more numerous, and can arise in less mature regions of the retina than rods, although both types of photoreceptors begin to express their respective opsins at about the same time. We applied these markers to an assay of cellular determination to identify the stages of embryonic development at which the earliest photoreceptor fates are induced in vivo. The relative birth order of the major cone and rod subtypes was revealed by simultaneous labeling with markers of cell proliferation and terminal differentiation. Although there is much temporal overlap between the periods of cone and rod genesis and determination in Xenopus, we could discern that the earliest cones are both born and determined before the first rods. Thus, even in the rapidly developing retina of Xenopus, photoreceptors achieve their identities in a sequential fashion, suggesting that the inductive cues which determine specific photoreceptor fates may also arise sequentially during development.

Amino Acid Sequence↗
PubMed1998

Absence of short-wavelength sensitive cones in the retinae of seals (Carnivora) and African giant rats (Rodentia).

Most non-primate mammals have two types of cone: short-wavelength sensitive (S) and middle-to-long-wavelength sensitive (M/L) cones. In two species of African giant rats, Cricetomys gambianus and C. emini, and in two species of earless seals, Phoca hispida and P. vitulina, the retinal cone types and cone distributions were assessed with antibodies specific for the M/L-cone opsin and the S-cone opsin, respectively. All four species were found to completely lack S-cones, while M/L-cones were present in low densities. M/L-cone densities, rod densities and cone/rod ratios were determined across the retina. Cone proportions are about 0.3-0. 5% in C. gambianus, 0.5-0.8% in C. emini, and 1.5-1.8% in P. hispida. An absence of S-cones has previously been reported in a few nocturnal mammals. As earless seals are visually active during night and day, we conclude that an absence of S-cones is not exclusively associated with nocturnality. The functional and comparative aspects are discussed.

Anatomy, Comparative↗
PubMed1997

Immunoreactive pinopsin in pineal and retinal photoreceptors of various vertebrates.

Pinopsin is a pineal specific opsin newly identified in the pineal of birds which has an absorption maximum at 470 nm. As the opsin content of photoreceptors in the pineal complex of several species is not yet known, in the present work, we studied their pinopsin immunoreactivity in various vertebrates from cyclostomes to mammals. We also compared the immunoreactivity of pineal photoreceptors to that of retinal cones and rods of each animal. For the immunocytochemistry, we raised antibodies in rabbits against a 14 amino acids containing part of the chicken pinopsin molecule. The immunoreaction was performed at the electron microscopic level. The pineal organs show a great diversity in vertebrates: there is a pineal organ present from cyclostomes to mammals, in addition, there is a parapineal organ in cyclostomes and fishes, a frontal organ in frogs and a parietal eye in several reptiles. We detected a strong pinopsin immunoreaction on most of the pinealocytes of birds and on the large photoreceptor-type of the pineal of reptiles. Rod-type photoreceptors of the avian retina and a cone of the reptile retina was immunoreactive as well. According to the known absorption maximum of pinopsin, the immunoreactivity may indicate a green-blue light-sensitivity for these photoreceptors. The immunoreactivity was less pronounced or absent in mammals as well as in less differentiated species. The pineal organ of snakes and the parietal eye of reptiles equally failed to exhibit pinopsin immunoreactive photoreceptors, presumably, due to the absence of green-blue light-sensitive photoreceptors of pinopsin-type in these species.

Animals↗
PubMed1999

Distribution and development of short-wavelength cones differ between Macaca monkey and human fovea.

Macaca monkey and humans have three cone types containing either long-wavelength (L), medium-wavelength (M), or short-wavelength (S)-specific opsin. The highest cone density is found in the fovea, which mediates high visual acuity. Most studies agree that the adult human fovea has a small S cone-free area, but data are conflicting concerning S-cone numbers in the adult Macaca monkey fovea, and little evidence exists for how either primate fovea develops its characteristic cone pattern. Single- and double-label in situ hybridization and immunocytochemistry have been used to determine the pattern of foveal S cones in both the fetal and adult Macaca and human. Both labels find a clear difference at all ages between monkey and human. Adult humans have a distinct but variable central zone about 100 microm wide that lacks S cones and is surrounded by a ring in which the S-cone density is 8%. This S cone-free zone is detectable at fetal week 15.5 (Fwk15.5), shortly after S opsin is expressed, and is similar to the adult by Fwk20.5. Adult monkey foveas have an overall S-cone foveal density of 10%, with several areas lacking a few S cones that are not coincident with the area of highest cone density. A surrounding zone at 200-microm eccentricity has an S-cone density averaging 25%, but, by 800 microm, this has decreased to 11%. Fetal day 77-135 monkeys all have a distribution and density of foveal S cones similar to adults, although the high-density ring is not obvious in fetal retinas. Estimates of the numbers of S cones missing in the fetal human fovea range from 234 to 328, whereas no more than 40 are missing in the fetal monkey. These results show that, in these two trichromatic primates, S-cone distribution and the developmental mechanisms determining S-cone topography are markedly different from the time that S cones are first detected.

Adult↗
PubMed2003

(9Z)- and (11Z)-8-methylretinals for artificial visual pigment studies: stereoselective synthesis, structure, and binding models.

Artificial visual pigment formation was studied by using 8-methyl-substituted retinals in an effort to understand the effect that alkyl substitution of the chromophore side chain has on the visual cycle. The stereoselective synthesis of the 9-cis and 11-cis isomers of 8-methylretinal, as well as the 5-demethylated analogues is also described. The key bond formations consist of a thallium-accelerated Suzuki cross-coupling reaction between cyclohexenylboronic acids and dienyliodides (C6-C7), and a highly stereocontrolled Horner-Wadsworth-Emmons or Wittig condensation (C11-C12). The cyclohexenylboronic acid was prepared by trapping the precursor cyclohexenyllithium species with B(OiPr)(3) or B(OMe)(3). The cyclohexenyllithium species is itself obtained by nBuLi-induced elimination of a trisylhydrazone (Shapiro reaction), or depending upon the steric hindrance of the ring, by iodine-metal exchange. In binding experiments with the apoprotein opsin, only 9-cis-5-demethyl-8-methylretinal yielded an artificial pigment; 9-cis-8-methylretinal simply provided residual binding, while evidence of artificial pigment formation was not found for the 11-cis analogues. Molecular-mechanics-based docking simulations with the crystal structure of rhodopsin have allowed us to rationalize the lack of binding displayed by the 11-cis analogues. Our results indicate that these isomers are highly strained, especially when bound, due to steric clashes with the receptor, and that these interactions are undoubtedly alleviated when 9-cis-5-demethyl-8-methylretinal binds opsin.

Binding Sites↗
PubMed1991

Arrestin mRNA expression, biosynthesis, and localization in degenerating photoreceptors of mutant rds mice retinas.

The retinal photoreceptors of the mutant rds mouse are unable to form normal outer segments. Eventually the abnormal cells die in the months following birth. The genetic defect in the rds mouse was recently localized to the peripherin gene that encodes a protein in the outer segment disc margin. Although this mutation may explain the morphogenetic defect, i.e., the failure to form outer segments, the reason for subsequent cell death is not clear. Previously, we demonstrated that the capability to synthesize opsin, an outer segment integral membrane protein, is not compromised by the morphogenetic defect although the opsin steady-state content is considerably reduced, since it is not incorporated into an organized outer segment. We have now studied arrestin, a cytoplasmic protein that is part of the phototransduction cascade and appears to shuttle between the inner and outer segment during the light/dark cycle. Since rds mice lack outer segments, it was of interest to determine the effects of the photoreceptor abnormality on arrestin gene expression. Arrestin mRNA levels and protein synthetic rates were high in young rds retinas. When corrected for cell loss, the steady-state arrestin content per cell in the rds retina was comparable to normal. However, in the absence of an outer segment, the total amount of arrestin is concentrated in the remaining inner segment. Consequently, a relatively high level of arrestin is present in the rds inner segment throughout the light/dark cycle. We suggest that the morphogenetic defect indirectly precipitates secondary effects such as the persistent presence of high levels of arrestin or other soluble proteins in the abnormal photoreceptor inner segment, nucleus, and synaptic terminal. This condition, if toxic to the cells, may compromise photoreceptor viability in the rds retina.

Animals↗
PubMed1992

Retinal growth and cell addition during embryogenesis in the teleost, Haplochromis burtoni.

Neurogenesis of the developing embryonic retina is described for the African cichlid fish, Haplochromis burtoni, from 4 days post fertilization until all cell phenotypes are generated (day 7). Cell addition and differentiation both begin at the same absolute location which later becomes the central retina. As observed in most other vertebrates, cones and ganglion cells differentiate first, followed by amacrine and bipolar cells. Rod photoreceptors, which are added late, differentiate last. Changes in retinal thickness, retinal stretching, cell size, and cell density were measured during development. From day 4 through 7, there is an increase in retinal thickness largely due to the expansion of the inner plexiform layer (IPL) and outer nuclear layer (ONL). The inner nuclear layer (INL) decreases in thickness and there is a transient decrease in the density of cells in the scleral portion of the INL. Cells increase in size in the ganglion cell layer (GCL) and the vitread INL, decrease in size in the sclerad INL, and remain the same in the ONL. Changes in the density of the cell layers were observed: the density of ONL cells increased, the density of GCL cells decreased, and INL cells increased then decreased. From day 4 to day 6, eye growth is entirely due to cell addition because no retinal stretching was observed in the ONL or the horizontal layer. During this same developmental period, the pattern and rate of neurogenesis were measured in the differentiated portion of the retina by means of 3H-thymidine labeling. A small number of cell divisions within the differentiated INL precede the onset of cell divisions in the ONL. The number of 3H-thymidine labeled cells within the INL increases at a low rate consistent with an asymmetric pattern of cell division characteristic of stem cells. In contrast, cell divisions in the ONL increase exponentially, consistent with a symmetric pattern of cell division characteristic of progenitor cells. Double-label experiments (3H-thymidine and a rod specific opsin antibody) show that some of the symmetrically dividing cells in the ONL express the rod specific opsin within 2 days, suggesting that these dividing cells are rod progenitors. Although we do not hae conclusive evidence, these developmental processes support the hypothesis that stem cells within the INL could be the source of rod precursors in the embryonic teleost retina.

Animals↗
PubMed1995

Why ontogeny recapitulates phylogeny.

In development, mammalian embryos successively develop notochord, somites, gill pouches and three sets of kidneys: pronephros, mesonephros and metanephros. Hence, Ernst Haeckel's dictum "ontogeny recapitulates phylogeny." The reason for this dictum appears to be the immortality of genes. Genes, once well entrenched, appear to linger for a long time even after the forfeiture of their raison d'être. The genes for dental enamel and dentin of the chicken are good examples. Furthermore, genes once doomed may resurrect themselves. For example, genes for red and green opsins of higher primates arose as alleles of the once doomed but resurrected red opsin locus.

Amino Acid Sequence↗
PubMed2001

Comparative ultrastructure and cytochemistry of the avian pineal organ.

The breeding of birds is expected to solve problems of nourishment for the growing human population. The function of the pineal organ synchronizing sexual activity and environmental light periods is important for successful reproduction. Comparative morphology of the avian pineal completes data furnished by experiments on some frequently used laboratory animals about the functional organization of the organ. According to comparative histological data, the pineal of vertebrates is originally a double organ (the "third" and the "fourth eye"). One of them often lies extracranially, perceiving direct solar radiation, and the other, located intracranially, is supposed to measure diffuse brightness of the environment. Birds have only a single pineal, presumably originating from the intracranial pineal of lower vertebrates. Developing from the epithalamus, the avian pineal organ histologically seems not to be a simple gland ("pineal gland") but a complex part of the brain composed of various pinealocytes and neurons that are embedded in an ependymal/glial network. In contrast to organs of "directional view" that develop large photoreceptor outer segments (retina, parietal pineal eye of reptiles) in order to decode two-dimensional images of the environment, the "densitometer"-like pineal organ seems to increase their photoreceptor membrane content by multiplying the number of photoreceptor perikarya and developing follicle-like foldings of its wall during evolution ("folded retina"). Photoreceptor membranes of avian pinealocytes can be stained by antibodies against various photoreceptor-specific compounds, among others, opsins, including pineal opsins. Photoreceptors immunoreacting with antibodies to chicken pinopsin were also found in the reptilian pineal organ. Similar to cones and rods representing the first neurons of the retina in the lateral eye, pinealocytes of birds possess an axonal effector process which terminates on the vascular surface of the organ as a neurohormonal ending, or forms ribbon-containing synapses on pineal neurons. Serotonin is detectable immunocytochemically on the granular vesicles accumulated in neurohormonal terminals. Pinealocytic perikarya and axon terminals also bind immunocytochemically recognizable excitatory amino acids. Peripheral autonomic fibers entering the pineal organ through its meningeal cover terminate near blood vessels. Being vasomotor fibers, they presumably regulate the blood supply of the pineal tissue according to the different levels of light-dependent pineal cell activity.

Animals↗
PubMed1975

Photoreceptor processes: some problems and perspectives.

Visual photoreceptors from both vertebrates and invertebrates are characterized by extensive elaboration of membrane which contains visual pigment (rhodopsin). Visual pigments in all phyla examined are chemically similar: the chromophore is 11-cis retinaldehyde attached by an aldimine linkage (Schiff base) to a membrane protein, opsin. The effect of light is to isomerize the chromophore to the all-trans configuration. Beyond these fundamental similarities, several specific areas are discussed in which variations and differences appear. (1) Light causes vertebrate visual pigments to bleach, liberating the chromophore. Most invertebrate visual pigments do not bleach in the light, but instead form a thermally stable metarhodopsin, with the chromophore in the all-trans configuration still attached to the opsin. (2) In the disk membranes of vertebrate rod and cone outer segments, the rhodopsin molecules are oriented with their chromophores nearly coplanar with the disks. Within this plane, however, both rotational and translational diffusion are possible. In the microvillar membranes of arthropod and cephalopod rhabdoms, on the other hand, the situation is less clear. There is evidence for some preferential orientation of chromophores that implies restrictions on Brownian rotation. (3) In the outer segments of vertebrate receptors, absorption of light by rhodopsin causes the plasma membrane to hyperpolarize due to a decrease in sodium conductance, possibly mediated by calcium ions. In most invertebrate photoreceptors, light causes a depolarization due to an increase in conductance, principally to sodium ions. A subsequent entry of calcium causes a partial repolarization of the membrane, due to a decrease in sodium conductance. (4) For vertebrate receptors, log threshold is directly proportional to the fraction of rhodopsin bleached (Dowling-Rushton relationship). The proportionality constant varies in different preparations from less than four to more than 30, and the physical basis for the relationship is unknown. For invertebrates, by contrast, the dependence of sensitivity on rhodopsin concentration is much less dramatic and may well depend simply on the probability of quantum catch. (5) In most species, vertebrate and invertebrate, the accumulation of photoproduct probably has no effect on membrane conductance, but several possible exceptions exist. (6) Photoregeneration of rhodopsin from metarhodopsin is likely an important mechanism of recovery in certain arthropods such as diurnal insects, but dark mechanisms of recovery also exist in all phyla. In no single case are they adequately understood.

Adaptation, Ocular↗
PubMed1977

The amino- and carboxyl-terminal sequence of bovine rhodopsin.

The amino terminus of bovine rhodopsin is blocked and has the sequence x-Met-Asn(CHO)-Gly-Thr-Glu-Gly-Pro-Asn-Phe-Tyr-Val-Pro-Phe-Ser-Asn(CHO)-Lys-Thr-Gly-Val-Val-Arg, where CHO represents sites of carbohydrate attachment. The carboxyl-terminal sequence of rhodopsin is Val-Ser-Lys-Thr-Glu-Thr-Ser-Gln-Val-Ala-Pro-Ala. Upon short-term digestion of rod outer segment (ROS) membranes with thermolysin, opsin (similar to 35,000 daltons) is converted to a membrane-bound fragment O' (similar to 30,500 daltons) and 2 peptides containing 12 amino acids are released from the carboxyl terminus of rhodopsin into the supernatant. Upon long-term digestion of ROS with thermolysin, opsin and O' are replaced by the membrane-bound fragments F1 (similar to 25,000 daltons), and F2 (similar 9,500 daltons). When 32P-ROS are digested, F2 carries the 32P. Both O' and F1 contain the amino-terminal glycopeptide.

Amino Acid Sequence↗
PubMed2006

Overview of retinoid metabolism and function.

Retinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all-trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all-trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra-nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein-coupled transmembrane receptors called opsins. These receptors function as light-driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin-bound 11-cis-retinal is isomerized to all-trans-retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all-trans retinol to all-trans retinal and all-trans retinoic acid, and esterification of all-trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all-trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life.

Animals↗
PubMed1989

Involvement of the Golgi apparatus in sorting of materials to opposite ends of frog rod retinal photoreceptors.

We have studied the rod cells of retinas of Rana pipiens by phosphatase cytochemistry and immunocytochemistry. We find that the Golgi apparatus of these cells, although different in its intracellular distribution from that of other neurons, has a cis-trans organization like that of other neurons as regards morphological features and the distribution of phosphatase activities. Antibodies against opsin bind to several sacs of the rod Golgi apparatus, especially those at the trans side of the Golgi stack. This suggests that Golgi involvement in the packaging of opsin for eventual delivery to the photoreceptive outer segments of the cell involves passage through trans Golgi systems. Proteins destined for the opposite end of the cell--the presynaptic terminal--also seem to pass through trans Golgi systems, as is indicated both by immunocytochemical localization of the synaptic vesicle protein p38 (synaptophysin) and by the presence of thiamine pyrophosphatase activity in some of the synaptic vesicles. Our findings suggest that sorting of membrane proteins destined for opposite ends of the photoreceptor takes place in systems at or near the trans Golgi face.

Animals↗
PubMed1998

Erx, a novel retina-specific homeodomain transcription factor, can interact with Ret 1/PCEI sites.

Our previous studies on the transcriptional regulation of rod opsin gene expression had defined a strikingly conserved element, Ret 1/PCEI, present in the upstream regulatory regions of opsin and other photoreceptor-specific genes. This element interacts with a 40 kDa, developmentally regulated, retina-specific protein. In this study we report the cloning of the novel retina-specific homeodomain protein Erx. Erx contains a homeodomain that is 79% homologous to that of Drosophila empty spiracles. This 40 kDa protein can interact with the Ret 1 element in electrophoretic mobility shift assays. Mutation of key residues in Ret 1 eliminates all Erx binding. Transient transfection of Y79 retinobalstoma cells with Erx leads to significant transcriptional activation of a reporter gene via Ret 1 elements. We conclude that Erx is the Ret 1 binding activity. This is the first example of a Q50 homeodomain protein expressed in retinal photoreceptors.

Amino Acid Sequence↗
PubMed1993

Photoreceptor degeneration in vitamin A deprivation and retinitis pigmentosa: the equivalent light hypothesis.

Long-term exposure of the retina to constant illumination is known to produce irreversible degeneration of photoreceptors. We propose that similar mechanisms may be involved in photoreceptor degeneration produced by vitamin A deprivation and some forms of retinitis pigmentosa (RP). Evidence is reviewed suggesting that the free opsin present during vitamin A deprivation or the mutated opsin present in some forms of RP excite the visual transduction cascade. This would produce a constant 'equivalent light' that triggers photoreceptor degeneration. Continuous real or equivalent light may produce outer segment degeneration by interfering with circadian processes, such as protein synthesis and disc shedding and lead to the loss of photoreceptors including those not expressing the mutant gene.

Animals↗