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PubMed2001

The molecular basis for spectral tuning of rod visual pigments in deep-sea fish.

Most species of deep-sea fish possess of a rod-only retina with a pigment that is generally shortwave shifted in lambda(max) towards the blue region of the spectrum. In addition, the lambda(max) values of different species tend to cluster at particular points in the spectrum. In this study, the rod opsin gene sequences from 28 deep-sea fish species drawn from seven different Orders are compared. The lambda(max) values of the rod pigments vary from approximately 520 nm to <470 nm, with the majority lying between 490 nm and 477 nm. The 520 nm pigment in two species of dragon fish is associated with a Phe261Tyr substitution, whereas the shortwave shifts of the pigments in the other 26 species are accountable by substitutions at a further eight sites (83, 122, 124, 132, 208, 292, 299 and 300). Clustering of lambda(max) values does not, however, involve a common subset of these substitutions in the different species. A phylogenetic analysis predicts that the pigment in the ancestral species would have had a lambda(max) of approximately 480 nm. A total of 27 changes is required to generate the pattern of substitutions seen in the different species, with many sites undergoing multiple changes.

Amino Acid Sequence↗

PubMed2003

Basic fibroblast and epidermal growth factors stimulate survival in adult porcine photoreceptor cell cultures.

PURPOSE: To investigate the effects of basic fibroblast and epidermal growth factor (FGF2 and EGF, respectively) on the survival and phenotypic expression of photoreceptors isolated from adult mammalian retinas. METHODS: Primary cultures highly enriched in photoreceptors were prepared from adult domestic pig retinas and maintained in chemically defined medium. Cell culture composition was characterized through the use of specific antibody markers of retinal neurons, and neuronal survival was quantified through viability assays as a function of time in the presence or absence of different doses of FGF2 and EGF. Western blot analysis of phosphotyrosine residues was used to monitor activation of FGF2 and EGF signaling pathways. RESULTS: Reproducible survival of adult pig rod and cone photoreceptors was obtained for approximately 2 weeks in vitro, with the continued expression of rod opsin, recoverin, S-antigen, cone arrestin, and neuron-specific enolase. Purity of cultures was routinely more than 95% photoreceptors, with a rod-cone ratio of 2:3.1. Photoreceptor survival was stable for the initial week, decreasing slowly during the second, with rapid cell loss occurring thereafter. In the presence of FGF2 (20 ng/mL), the percentage of photoreceptor survival during the second week in culture was statistically significantly different, at least two times higher than in control experiments. Photoreceptor survival correlated directly with increasing concentrations of FGF2, and also of EGF. Combined treatment with FGF2 and EGF did not induce higher survival than either factor alone. There was no detectable selective loss of rods or cones in the experimental model. Phosphotyrosine immunoblots after stimulation of cultures with FGF2 and EGF revealed time-dependent appearance of multiple immunoreactive bands. CONCLUSIONS: The adult pig photoreceptor culture in the current study exhibits reproducible neuronal survival in vitro and represents a useful novel experimental system for the study of potential neuroprotective effects and signaling pathways of neurotrophic factors such as FGF2 and EGF in fully adult higher mammalian retina.

Animals↗

PubMed2003

Molecular cloning and characterization of rhodopsin in a teleost (Plecoglossus altivelis, Osmeridae).

Amplified fragments encoding exon-4 of opsin cDNAs were cloned from the retina of landlocked ayu (Plecoglossus altivelis), and sequenced. On the basis of the sequence homology to previously characterized fish visual pigments, one clone was identified as rod opsin (AYU-Rh), and two clones as green (AYU-G1, -G2), one as red (AYU-R) and two as ultraviolet (AYU-UV1, -UV2) cone opsins. The 335-amino acid sequence deduced from the full-length cDNA of AYU-Rh included residues highly conserved in vertebrate rhodopsins and showed the greatest degree (88%) of similarity with salmon rhodopsin. Southern blotting analysis indicated that ayu possess two rhodopsin genes, one encoding visual rhodopsin (AYU-Rh) and the other non-visual extra-ocular rhodopsin (AYU-ExoRh). RT-PCR experiments revealed that AYU-Rh was expressed in the retina and AYU-ExoRh in the pineal gland. In situ hybridization experiments showed that the mRNA of AYU-Rh was localized only in rod cells not in cone cells. Lake and river type landlocked ayu having different amounts of retinal and 3-hydroxyretinal in their retinas expressed a rhodopsin (AYU-Rh) of identical amino acid sequence.

Base Sequence↗

PubMed2003

Gene duplication and spectral diversification of cone visual pigments of zebrafish.

Zebrafish is becoming a powerful animal model for the study of vision but the genomic organization and variation of its visual opsins have not been fully characterized. We show here that zebrafish has two red (LWS-1 and LWS-2), four green (RH2-1, RH2-2, RH2-3, and RH2-4), and single blue (SWS2) and ultraviolet (SWS1) opsin genes in the genome, among which LWS-2, RH2-2, and RH2-3 are novel. SWS2, LWS-1, and LWS-2 are located in tandem and RH2-1, RH2-2, RH2-3, and RH2-4 form another tandem gene cluster. The peak absorption spectra (lambdamax) of the reconstituted photopigments from the opsin cDNAs differed markedly among them: 558 nm (LWS-1), 548 nm (LWS-2), 467 nm (RH2-1), 476 nm (RH2-2), 488 nm (RH2-3), 505 nm (RH2-4), 355 nm (SWS1), 416 nm (SWS2), and 501 nm (RH1, rod opsin). The quantitative RT-PCR revealed a considerable difference among the opsin genes in the expression level in the retina. The expression of the two red opsin genes and of three green opsin genes, RH2-1, RH2-3, and RH2-4, is significantly lower than that of RH2-2, SWS1, and SWS2. These findings must contribute to our comprehensive understanding of visual capabilities of zebrafish and the evolution of the fish visual system and should become a basis of further studies on expression and developmental regulation of the opsin genes.

Amino Acid Sequence↗

PubMed2006

Functional characterization of visual opsin repertoire in Medaka (Oryzias latipes).

A variety of visual pigment repertoires present in fish species is believed due to the great variation under the water of light environment. A complete set of visual opsin genes has been isolated and characterized for absorption spectra and expression in the retina only in zebrafish. Medaka (Oryzias latipes) is a fish species phylogenetically distant from zebrafish and has served as an important vertebrate model system in molecular and developmental genetics. We previously isolated a medaka rod opsin gene (RH1). In the present study we isolated all the cone opsin genes of medaka by genome screening of a lambda-phage and bacterial artificial chromosome (BAC) libraries. The medaka genome contains two red, LWS-A and LWS-B, three green, RH2-A, RH2-B and RH2-C, and two blue, SWS2-A and SWS2-B, subtype opsin genes as well as a single-copy of the ultraviolet, SWS1, opsin gene. Previously only one gene was believed present for each opsin type as reported in a cDNA-based study. These subtype opsin genes are closely linked and must be the products of local gene duplications but not of a genome-wide duplication. Peak absorption spectra (lambda(max)) of the reconstituted photopigments with 11-cis retinal varied greatly among the three green opsins, 452 nm for RH2-A, 516 nm for RH2-B and 492 nm for RH2-C, and between the two blue opsins, 439 nm for SWS2-A and 405 nm for SWS2-B. Zebrafish also has multiple opsin subtypes, but phylogenetic analysis revealed that medaka and zebrafish gained the subtype opsins independently. The lambda and BAC DNA clones isolated in this study could be useful for investigating the regulatory mechanisms and evolutionary diversity of fish opsin genes.

Animals↗

PubMed2006

Does recombinant adeno-associated virus-vectored proximal region of mouse rhodopsin promoter support only rod-type specific expression in vivo?

PURPOSE: We have previously found that the -385 to +86 portion of the mouse rod opsin promoter (mOP500) can limit recombinant adeno-associated virus (rAAV)-mediated transgene expression to photoreceptor cells when delivered subretinally. However, the photoreceptor (PR) subtype-specificity of expression remains unclear. Here, we evaluated whether the presence of certain cis-elements in this proximal promoter, such as the rod-specific, neural retina leucine zipper protein (NRL) response element (NRE), can render it a driver of rod-specific expression. METHODS: Subretinal injections of a serotype 5 rAAV vector carrying the green fluorescent protein (GFP) cDNA, driven by mOP500, were administered to male Sprague-Dawley rats at postnatal day (P) 40-48. Two weeks to eight months later, the distribution of GFP-expressing cells in the retina was characterized by GFP-, cone-specific alpha-transducin-immuno-, and peanut agglutinin-lectin histochemistry and by morphological criteria. The same viral suspension was also injected sub-retinally into rhodopsin-knockout rho (-/-) mice either at P18 or P78, and retinas were analyzed by immunohistochemistry and PNA lectin histochemistry two weeks later. RESULTS: GFP reactivity was found exclusively in the outer nuclear layer (ONL) of rat retinas two weeks after treatment, with abundant reporter gene expression observed in both rods and cones. GFP-positive cones, defined by their typical morphology and the co-linearity of PNA-lectin labeling with GFP-immunoreactivity, were found in all regions of the transduced retinas. GFP-positive cones constituted up to 6% of the total GFP-positive photoreceptors. By eight months post-injection, a low level of GFP-reactivity was additionally observed in the inner nuclear layer (INL) and ganglion cell layer. Photoreceptor-specific GFP expression was also seen in the rho (-/-) mice at both ages tested. In pups injected at P18, costaining with PNA-lectin revealed that up to 15% of the GFP-positive photoreceptors were cones. Despite only a single row of photoreceptors remaining in these knockout mice by P90, numerous GFP-positive cones were still present. CONCLUSIONS: Subretinal delivery of rAAV5 harboring a reporter gene driven by mOP500 results in passenger gene expression in both rod and cones, indicating that this promoter is photoreceptor-specific but not rod-specific. The lack of photoreceptor subtype-specificity suggests that although cones do not express the NRL and NR2E3 trans-factors considered necessary for activation of mOP500, other general transcription factors in cones may compensate.

Animals↗

PubMed1991

Circadian photoreception in the retinally degenerate mouse (rd/rd).

We have examined the effects of light on circadian locomotor rhythms in retinally degenerate mice (C57BL/6J mice homozygous for the rd allele: rd/rd). The sensitivity of circadian photoreception in these mice was determined by varying the irradiance of a 15 min light pulse (515 nm) given at circadian time 16 and measuring the magnitude of the phase shift of the locomotor rhythm. Experiments were performed on animals 80 days of age. Despite the loss of visual photoreceptors in the rd/rd retina, animals showed circadian responses to light that were indistinguishable from mice with normal retinas (rd/+ and +/+). While no photoreceptor outersegments were identified in the retina of rd/rd animals (80-100 days of age), we did identify a small number of perikarya that were immunoreactive for cone opsins, and even fewer cells that contained rod opsin. Using HPLC, we demonstrated the presence and photoisomerization of the rhodopsin chromophore 11-cis retinaldehyde. The rd/rd retinas contained about 2% of 11-cis retinaldehyde found in +/+ retinas. We have yet to determine whether the opsin immunoreactive perikarya or some other unidentified cell type mediate circadian light detection in the rd/rd retina.

Animals↗

PubMed2006

Proteomic analysis of opsins and thyroid hormone-induced retinal development using isotope-coded affinity tags (ICAT) and mass spectrometry.

PURPOSE: Analyses that reveal the relative abundance of proteins are informative in elucidating mechanisms of retinal development and disease progression. However, popular high-throughput proteomic methods do not reliably detect opsin protein abundance, which serve as markers of photoreceptor differentiation. We utilized thyroid-hormone (TH) treatment of rainbow trout (Oncorhynchus mykiss) as a model of cone apoptosis and cone regeneration. We used this model to investigate if emerging proteomic technology allows effective analysis of retinal development and opsin protein abundance. We also sought to begin a characterization of proteomic changes in the retina occurring with TH treatment and address whether TH affects proliferation or photoreceptor differentiation. METHODS: Retinal homogenates were prepared from control and TH-treated fish. Peptides from control and treated homogenates were differentially labeled, using isotope-code affinity tags (ICAT) and analyzed using capillary liquid chromatography-electrospray ionization-tandem mass spectrometry (capLC-ESI-MS/MS). This method identifies proteins and quantifies their relative abundance between two samples. RESULTS: The relative abundance of many retinal proteins changed during TH treatment. These included proteins from every functional class. We detected 1,684 different peptides, and our quantification suggests that 94 increased and 146 decreased in abundance more than 50% during TH treatment. Cell-cycle proteins appear to be increased, consistent with TH-inducing cell proliferation, similar to its effect in Xenopus. Other proteins associated with retinal development, such as deltaA and tubulins, changed in abundance during TH treatment. Rod opsin and three cone opsins were identified and the relative abundance of each changed with TH treatment. CONCLUSIONS: ICAT and capLC-ESI-MS/MS are an effective complement to other molecular approaches that investigate the mechanisms of retinal development. Unlike other proteomic techniques, this approach does not require development of species- or tissue-specific methodology, such as characterizing two dimensional (2D) gels or antibodies, in order to be practical as a high-throughput approach. Importantly, this technology was able to assess the relative abundance of opsin proteins. These findings represent the first high-throughput proteomic analysis of the retina and demonstrate the technique's ability to provide useful information in retinal development.

Animals↗

PubMed1998

Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa.

Ribozymes, catalytic RNA molecules that cleave a complementary mRNA sequence, have potential as therapeutics for dominantly inherited disease. Twelve percent of American patients with the blinding disease autosomal dominant retinitis pigmentosa (ADRP) carry a substitution of histidine for proline at codon 23 (P23H) in their rhodopsin gene, resulting in photoreceptor cell death from the synthesis of the abnormal gene product. Ribozymes can discriminate and catalyze the in vitro destruction of P23H mutant mRNAs from a transgenic rat model of ADRP. Here, we demonstrate that in vivo expression of either a hammerhead or hairpin ribozyme in this rat model considerably slows the rate of photoreceptor degeneration for at least three months. Catalytically inactive control ribozymes had less effect on the retinal degeneration. Intracellular production of ribozymes in photoreceptors was achieved by transduction with a recombinant adeno-associated virus (rAAV) incorporating a rod opsin promoter. Ribozyme-directed cleavage of mutant mRNAs, therefore, may be an effective therapy for ADRP and also may be applicable to other inherited diseases.

Animals↗

PubMed2004

Expression of the candidate circadian photopigment melanopsin (Opn4) in the mouse retinal pigment epithelium.

A number of responses to light, including circadian entrainment and pupillary constriction, are preserved in mammals that lack rod and cone photoreceptors. Recent studies have demonstrated that a subset of retinal ganglion cells (RGCs) are intrinsically photosensitive, and that these RGCs project to regions of the brain associated with the regulation of the circadian clock and pupil constriction. The photopigment gene(s) that mediate these effects of irradiance remain unidentified, although melanopsin (Opn4) has emerged as a strong candidate. For example, Opn4 is expressed within intrinsically photosensitive RGCs, and Opn4 knock-out mice show attenuated circadian and pupillary responses to light. In this study we provide the first clear evidence that Opn4 expression is not confined to these photosensitive RGCs, but is also expressed in the retinal pigment epithelium (RPE), a tissue with no known photosensensory role. We can preclude retinal contamination of RPE extracts as levels of Opn4 expression were higher in the RPE than in the retina, and the expression of rod opsin and Thy1 (a marker of the RGC layer) were barely detectable in RPE extracts. Our results raise questions about the presumed function of melanopsin, and highlight the need for biochemical studies on this protein.

Animals↗

PubMed1996

Spectral tuning and molecular evolution of rod visual pigments in the species flock of cottoid fish in Lake Baikal.

Lake Baikal in Eastern Siberia is the deepest and one of the largest and most ancient lakes in the world. However, even in the deepest regions, oxygenation levels do not fall below 75-80% of the surface levels. This has enabled a remarkable flock of largely endemic teleost fish of the sub-order Cottoidei to colonize all depth habitats. We have previously shown that species that occupy progressively deeper habitats show a blue shift in the peak wavelength of absorbance (lambda max) of both their rod and cone visual pigments; for the rod pigments, a number of stepwise shifts occur from about 516 nm in littoral species to about 484 nm in abyssal species. By sequencing the rod opsin gene from 11 species of Baikal cottoids that include representatives from all depth habitats, we have been able to identify four amino acid substitutions that would account for these shifts. The effect of each substitution on lambda max is approximately additive and each corresponds to a particular lineage of evolution.

Amino Acid Sequence↗

PubMed2004

Identification of extraretinal photoreceptors in the teleost Phoxinus phoxinus.

The existence of cells capable of detecting changes of the photoperiod within the deep brain, the so-called deep brain photoreceptors, was proposed in the early years of the twentieth century. By using immunocytochemistry with antisera against phototransductory proteins on paraffin and vibratome sections, we have localized several positive areas in the brain of the teleost Phoxinus phoxinus. These areas were restricted to two encephalic regions: the epithalamus and the hypothalamus. Immunopositive (rod-opsin- and a-transducin-like) pinealocytes and parapinealocytes, as well as some sparse neurons in the habenula, were seen in the epithalamus. The immunoreaction of the hypothalamus was represented by a-transducin-like positive (magnocellular and parvicellular) neurons of the Nucleus Preopticus, as well as by a-transducin- and arrestin-like positive fibers corresponding to the hypothalamic-hypophyseal tract and a few fibers running towards the basal telencephalon. These findings corroborate the data published on other teleost fish and fully support the hypothesis of the presence of photosensitive cells in the encephalon of lower vertebrates. The labelling with antisera against different components of the phototransductory cascade also strengthens the idea that such cells employ a biochemical mechanism similar to that in the retinal visual photoreceptor cells, rods and cones. Although the function is still unclear, the detection of the photoperiod seems to be the most likely role for these extraretinal photoreceptors.

Animals↗

PubMed1993

Differential expression of retinal proteins in a pineal parenchymal tumor.

The pineal gland and retina share histogenetic features that reflect a similar neurosensory/photosensory ontogeny. Pineal parenchymal tumors demonstrate a highly variable and incomplete photosensory differentiation evidenced by specific cytoarchitectural features and the expression of photosensory retinal S-Antigen (S-Ag). Despite these neuro-ontogenetic parallels, pineal parenchymal tumors have not been well studied for the neuroretinal phenotypes that accompany normal neuroretinal development. The investigation of photoreceptor gene expression may provide an important insight into the histogenesis of pineal parenchymal neoplasms. In this study, a pineal parenchymal tumor of the "mixed pineoblastoma/pineocytoma" type was examined for the expression of several photoreceptor, glial and neuronal proteins including: interphotoreceptor retinoid-binding protein (IRBP), rod opsin, cone opsin, S-Ag and cellular retinaldehyde-binding protein (CRA1BP). The detection of IRBP and its mRNA, the earliest photoreceptor-associated protein expressed during retinal development, corroborated the rudimentary photosensory differentiation of this tumor which had limited cytoarchitectural evidence for pineal differentiation. The analysis of IRBP expression may facilitate the diagnostic recognition of primitive pineal neoplasms and further define the neuroretinal differentiation which occurs in pineal parenchymal tumors.

Adolescent↗

PubMed2003

Proapoptotic bcl-2 family members, Bax and Bak, are essential for developmental photoreceptor apoptosis.

PURPOSE: Apoptosis has been implicated in retinal development and degeneration, but the specific apoptotic pathways used are incompletely understood. The purpose of this study was to characterize the roles in retinal development of the proapoptotic Bcl-2 family members Bax and Bak. METHODS: Eyes from mice at postnatal day (P)7, during the peak of developmental apoptosis in the retina, were processed for TdT-dUTP terminal nick-end labeling (TUNEL) to determine whether Bax knockout or double Bax/Bak knockout causes a defect in developmental apoptosis. Adult (>2-month-old) eyes from wild-type, Bak(-/-), Bax(-/-), and Bax(-/-)Bak(-/-) mice were analyzed by histology and immunocytochemistry to identify persistent retinal cells. RESULTS: Adult Bax(-/-)Bak(-/-) eyes showed significant increases in the number of inner retinal cells, with an almost complete absence of TUNEL-positive cell death at P7. Some of these persistent cells in the inner retina notably included rod photoreceptors that normally undergo apoptosis after failure to migrate to the outer retina. These inner nuclear layer (INL) rods contained markers of early rod differentiation: rod opsin, arrestin, and recoverin. However, they did not form ectopic outer segments or contain the associated markers ROM-1, peripherin-2, and RP1. CONCLUSIONS: Bax and Bak are important for retinal development and are the first apoptotic factors identified as essential for developmental photoreceptor apoptosis. Future studies will investigate the potential role of Bax and Bak in mediating pathologic photoreceptor death.

Animals↗

PubMed1999

Time-resolved rhodopsin activation currents in a unicellular expression system.

The early receptor current (ERC) is the charge redistribution occurring in plasma membrane rhodopsin during light activation of photoreceptors. Both the molecular mechanism of the ERC and its relationship to rhodopsin conformational activation are unknown. To investigate whether the ERC could be a time-resolved assay of rhodopsin structure-function relationships, the distinct sensitivity of modern electrophysiological tools was employed to test for flash-activated ERC signals in cells stably expressing normal human rod opsin after regeneration with 11-cis-retinal. ERCs are similar in waveform and kinetics to those found in photoreceptors. The action spectrum of the major R(2) charge motion is consistent with a rhodopsin photopigment. The R(1) phase is not kinetically resolvable and the R(2) phase, which overlaps metarhodopsin-II formation, has a rapid risetime and complex multiexponential decay. These experiments demonstrate, for the first time, kinetically resolved electrical state transitions during activation of expressed visual pigment in a unicellular environment (single or fused giant cells) containing only 6 x 10(6)-8 x 10(7) molecules of rhodopsin. This method improves measurement sensitivity 7 to 8 orders of magnitude compared to other time-resolved techniques applied to rhodopsin to study the role particular amino acids play in conformational activation and the forces that govern those transitions.

Cell Fusion↗

PubMed2003

Ontogeny of ultraviolet-sensitive cones in the retina of rainbow trout (Oncorhynchus mykiss).

In order to facilitate emerging models of retinal development, we developed electroretinogram and in situ hybridization protocols to examine the ontogeny of photoreceptors in the retina of a land-locked salmonid, the rainbow trout (Oncorhynchus mykiss). We cloned cDNA fragments corresponding to the rod opsin and each of the four cone opsin gene families, which we utilized to produce riboprobes. We established the specificity of the in situ hybridization protocol by examining subcellular signal localization and through double-labeling experiments. We confirm the assumption that the accessory corner cones in the square mosaic are the ultraviolet wavelength-sensitive (UVS) cone photoreceptor (i.e., they express an SWS1 opsin) and observed UVS cones throughout the retina of small trout. Larger fish have a decrease in sensitivity to short wavelength light stimuli and the distribution of UVS cones in the mature retina is limited to the dorsal-temporal quadrant. These larger fish also possess differentiated UVS cones in the peripheral germinal zone (PGZ), including within areas peripheral to mature retina lacking UVS cones. These data are consistent with the loss of putative UVS cones from the PGZ of a migratory salmonid of another genus, and thus the disappearance of UVS cones appears to be general to the Family Salmonidae, regardless of life history strategy. The generation, differentiation, and subsequent loss of UVS cones in the smolt PGZ is a dramatic example of the supposition that the mechanisms of PGZ development recapitulate the retinal embryogenesis of that species.

Aging↗

PubMed2002

Developmental death of photoreceptors in the C57BL/6J mouse: association with retinal function and self-protection.

We have investigated the relationship between cell death among photoreceptors and the expression of function- and stress-related proteins during the development of the retina of the C57BL/6J mouse. Retinas from mice aged P(postnatal day)4 to P63 (adult) were examined for cell death using the TUNEL technique, and for the expression of basic fibroblast growth factor (bFGF), cytochrome oxidase (CO), rod opsin and glial fibrillary acidic protein (GFAP), using immunocytochemistry. At P4, cell death is most prominent in the inner layers of retina, declining to near-zero levels by P16. Cell death among photoreceptors occurs in a discrete wave commencing at approximately P12 and remaining elevated into the 4th postnatal week, beginning, peaking and declining later than in inner retina. The onset of photoreceptor death correlates with the expression of function-related molecules, such as CO and opsin. The decline in photoreceptor death correlates with the expression of the protective factor bFGF in photoreceptors. At the anterior edge of the retina photoreceptor death and the expression of bFGF are accelerated, and the expression of bFGF and GFAP is upregulated, by an edge-specific stress. We conclude that in the mouse photoreceptors undergo a wave of death which culls the neonatal population to adult levels. The onset of photoreceptor death is related to the acceleration of photoreceptor metabolism and function between P12 and P20. The decline of photoreceptor death to the very low levels found in the adult may be mediated by the upregulation of protective factors such as bFGF. Photoreceptor death and the expression of bFGF and GFAP at the edge of the retina are regulated by a still-unidentified, edge-specific stress, from as early as P16.

Aging↗

PubMed1996

Selective absence of cone outer segment beta 3-transducin immunoreactivity in hereditary cone degeneration (cd).

We have used immunocytochemistry and in situ hybridization to examine the expression of photoreceptor specific genes in retinas of normal dogs and those affected with hereditary cone degeneration (cd), a rare autosomal recessive disorder that selectively affects cones. In the cd retina, cone disease begins early in life; cones are lost by extrusion of the nucleus into the inner segment, and later by displacement of the nucleus, surrounded by a thin rim of cytoplasm, into the interphotoreceptor space. Two micrometer sections from the superior and inferior retinal meridians, extending from the optic disk to the ora serrata, were used for in situ hybridization with a bovine rod opsin and human red/green cone opsin cRNA probes, or were reacted with antibodies directed against photoreceptor-specific proteins and visualized with appropriate biotinylated antibodies. Antibodies against the following proteins were used: alpha- and beta 3-transducins, phosducin, alpha/beta- and gamma-phosphodiesterases, COS-1, and OS-2, opsin, S-antigen and IRBP. Immunoreactivity or hybridization labeling was evaluated in unstained sections; cone pathology was judged in adjacent Toluidine Blue-stained sections. With these methods it was possible to evaluate immunoreactivity or hybridization labeling and cone pathology at the single cell level. Both middle-(COS-1) and short-(OS-2) wavelength-sensitive cones were present in controls and cd affected retinae at 2.2 months, and distinct transcripts of the red/green cone pigment gene were identified in the majority of cones in both normal and affected retinas at this age. However, beta 3-transducin immunoreactivity was completely absent from cd-affected cone outer segments. Both cone types were present but in reduced numbers in older animals (11.5 and 17 months), and no reactivity to beta 3-transducin was noted. No differences were found with the other antibodies used. The specific absence of beta 3-transducin immunoreactivity from the cone outer segments suggests a potential involvement of the beta 3-transducin gene or gene product in the disease process.

Animals↗