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PubMed1980

Dark isomerization of retinals in the presence of phosphatidylethanolamine.

1. Dark incubation of retinoids (retinyl ester, retinol, retinal, retinaloxime) in suspensions of rod outer segment membranes leads to substantial isomerization (and partial degradation) in the case of retinals only. 2. All-trans, 13-cis and 9-cis-retinal all isomerize at the delta 13 double bond leading to an equilibrium with approximately 75% trans and 25% cis isomer at this bond (all-trans in equilibrium 13-cis and 9-cis in equilibrium 9,13-dicis). 11-cis-Retinal isomerizes irreversibly to a mixture of all-trans and 13-cis-retinal. 3. The active compound appears to be phosphatidylethanolamine present in the membrane. The amino group and the phosphate, as well as the hydrophobic part of the phospholipid are essential. 4. At least three factors are important for the phosphatidylethanolamine-catalyzed isomerization as studied with the 13-cis isomer: the concentration of phosphatidylethanolamine, the concentration of Schiff base between retinal and phosphatidylethanolamine and the presence of lipid aggregates. 5. Based on these observations a mechanism is proposed, which satisfactorily explains the specificity of the isomerization pattern. 6. It is suggested that reisomerization of all-trans to 11-cis retinal in vivo takes place by fixation of all-trans retinal on an adequate surface (e.g. opsin) and a localized nucleophilic attack on the C-11 atom, followed by trapping of the isomerized chromophore by opsin. 7. It is further concluded that retinal does not occur in vivo as a free intermediate. Direct transfer from one protein to another (opsin, retinol dehydrogenase, retinal binding proteins) seems to take place.

Catalysis↗
PubMed2004

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↗
PubMed1994

Shape of the chromophore binding site in pharaonis phoborhodopsin from a study using retinal analogs.

To investigate the shape of the chromophore binding site of pharaonis phoborhodopsin (ppR), ppR-opsin was incubated with five ring-modified retinal analogs: an acyclic retinal, phenylretinal, alpha-retinal, cyclohexylretinal and 5-isopropyl-alpha-retinal. The experimental results were compared with those obtained from bacteriorhodopsin-opsin (bR-opsin) and the same retinal analogs. It was suggested that ring chain conformation is important in affecting the spectral shoulder unique for the absorption spectrum of ppR. The rate of pigment formation depended greatly on the analogs used with the planar analogs showing rapid formation. Thus, we concluded that the space of the retinal binding site of ppR is restricted to the plane of the cyclohexenyl ring of the chromophore, whereas that of bR is less restricted.

Archaeal Proteins↗
PubMed1991

Expression of the bop gene cluster of Halobacterium halobium is induced by low oxygen tension and by light.

The bop gene cluster consists of at least three genes: bop (bacterio-opsin), brp (bacterio-opsin-related protein), and bat (bacterio-opsin activator). We have quantitated transcript levels from these genes in a wild-type and bacterioruberin-deficient mutant of Halobacterium halobium under conditions which affect purple membrane synthesis. In wild-type cultures grown under high oxygen tension in the dark, bop and bat transcript levels were low during steady-state growth and then increased approximately 29- and approximately 45-fold, respectively, upon entry into stationary phase. brp gene transcription remained very low and essentially unchanged under these conditions. In addition, exposure of wild-type cultures growing under high oxygen tension to 30,000 lx of light stimulated expression of all three genes, especially brp. In contrast to the wild-type, transcription from all three genes in the bacterioruberin mutant was very high during steady-state growth under high oxygen tension in the dark. Cultures of the bacterioruberin mutant were shifted at early stationary phase to low oxygen tension to determine whether oxygen concentrations lower than those present in stationary phase would induce transcription of the bop gene cluster in this strain. Indeed, transcription was induced, suggesting that the bop gene cluster is not completely uncoupled from regulation by oxygen tension in the bacterioruberin mutant. From these data, we propose a regulatory model involving two different mechanisms: (i) bat gene expression is induced under conditions of low oxygen tension and the bat gene product activates bop gene expression and (ii) light induces brp transcription, which stimulates or modulates bat transcription.

Bacteriorhodopsins↗
PubMed1994

bop gene cluster expression in bacteriorhodopsin-overproducing mutants of Halobacterium halobium.

mRNA levels from the bop (bacterio-opsin), brp (bacterio-opsin-related protein), and bat (bacterio-opsin activator) genes in wild-type Halobacterium halobium and two bacteriorhodopsin-overproducing mutants (ET1001 and II-7) were quantitated under conditions in which oxygen levels were steadily depleted and then cultures were either kept in the dark or exposed to light. All three strains showed similar responses to depleted oxygen tensions and the lack of light: bop gene cluster transcript levels first increased in response to steadily declining oxygen, and once oxygen was depleted, transcript levels decreased and became undetectable within 20 to 40 h. In contrast, each strain responded differently to conditions of depleted oxygen and the presence of light. In the wild-type strain, bop gene cluster transcript levels increased 2.4- to 9.2-fold above the highest levels obtained in the dark. In mutant ET1001, bop gene cluster transcript levels did not increase above the highest levels obtained in the dark. In mutant II-7, bop and brp transcript levels did not increase above the highest levels obtained in the dark, but bat transcript levels increased approximately 5.7-fold. This differing response to identical physiological conditions indicates that the mutations resulting in the bacteriorhodopsin-overproducing phenotype in these two mutants are different.

Bacteriorhodopsins↗
PubMed2003

Cone photoreceptor recovery after experimental detachment and reattachment: an immunocytochemical, morphological, and electrophysiological study.

PURPOSE: To compare the morphologic and functional recovery of the retina after detachment and reattachment in an animal with a cone-dominant retina, the ground squirrel. METHODS: Ground squirrel (Spermophilus beecheyi) retinas were detached for 1 day and reattached for 7, 35, or 96 days (n = 2, each time point). Flicker ERGs were recorded 1 day after the detachment and at various times after reattachment. Contrast-response functions were measured for isochromatic modulation and for selective modulation of short-wavelength-sensitive (S) and middle-wavelength-sensitive (M) cones. At the end of the experiment, retinas were prepared for light microscopy or immunocytochemical staining with antibodies to rod opsin, S and M cone opsins, cytochrome oxidase, synaptophysin, glial fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), interphotoreceptor-binding protein (IRBP), and peanut agglutinin lectin (PNA). Photoreceptor density maps were created from wholemount preparations labeled with biotinylated PNA and anti-S cone opsin. Cell counts of photoreceptor nuclei and cone outer segments (OS) were compared with flicker ERG data. Cell death was examined by the TUNEL method. RESULTS: Reattachment stopped photoreceptor cell death and reversed the disruption of interphotoreceptor matrix as well as the redistribution of Müller cell proteins. It also activated some astrocytes based on anti-GFAP staining. S- and M-cone OS showed a gradual recovery in length after reattachment, and this recovery continued to the longest time points examined. ERG contrast gains also recovered after reattachment, but these reached asymptotic levels by approximately a week after reattachment. There were significant correlations between outer nuclear layer (ONL) cell counts and ERG contrast gains. No differences were noted in the indices of recovery of M and S cones. CONCLUSIONS: The ERG can be used to follow specifically the changes in the retina that occur after retinal detachment and reattachment.

Animals↗
PubMed2005

Sexual dimorphism of short-wavelength photoreceptors in the small white butterfly, Pieris rapae crucivora.

The eyes of the female small white butterfly, Pieris rapae crucivora, are furnished with three classes of short-wavelength photoreceptors, with sensitivity peaks in the ultraviolet (UV) (lambda(max) = 360 nm), violet (V) (lambda(max) = 425 nm), and blue (B) (lambda(max) = 453 nm) wavelength range. Analyzing the spectral origin of the photoreceptors, we isolated three novel mRNAs encoding opsins corresponding to short-wavelength-absorbing visual pigments. We localized the opsin mRNAs in the retinal tissue and found that each of the short-wavelength-sensitive photoreceptor classes exclusively expresses one of the opsin mRNAs. We, accordingly, termed the visual pigments PrUV, PrV, and PrB, respectively. The eyes of the male small white butterfly also use three classes of short-wavelength photoreceptors that equally uniquely express PrUV, PrV, and PrB. However, whereas the spectral sensitivities of the male photoreceptors with PrUV and PrB closely correspond to those of the female, the male photoreceptor expressing PrV has a double-peaked blue (dB) spectral sensitivity, strongly deviating from the spectral sensitivity of the female V photoreceptor. The male eyes contain a pigment that distinctly fluoresces under blue-violet as well as UV excitation light. It coexists with the dB photoreceptors and presumably acts as a spectral filter with an absorbance spectrum peaking at 416 nm. The narrow-band spectral sensitivity of the male dB photoreceptors probably evolved to improve the discrimination of the different wing colors of male and female P. rapae crucivora in the short-wavelength region of the spectrum.

Animals↗
PubMed2001

Constitutive "light" adaptation in rods from G90D rhodopsin: a mechanism for human congenital nightblindness without rod cell loss.

A dominant form of human congenital nightblindness is caused by a gly90-->asp (G90D) mutation in rhodopsin. G90D has been shown to activate the phototransduction cascade in the absence of light in vitro. Such constitutive activity of G90D rhodopsin in vivo would desensitize rod photoreceptors and lead to nightblindness. In contrast, other rhodopsin mutations typically give rise to nightblindness by causing rod cell death. Thus, the proposed desensitization without rod degeneration would be a novel mechanism for this disorder. To explore this possibility, we induced mice to express G90D opsin in their rods and then examined rod function and morphology, after first crossing the transgenic animals with rhodopsin knock-out mice to obtain appropriate levels of opsin expression. The G90D mouse opsin bound the chromophore and formed a bleachable visual pigment with lambda(max) of 492 nm that supported rod photoresponses. (G+/-, R+/-) retinas, heterozygous for both G90D and wild-type (WT) rhodopsin, possessed normal numbers of photoreceptors and had a normal rhodopsin complement but exhibited considerable loss of rod sensitivity as measured electroretinographically. The rod photoresponses were desensitized, and the response time to peak was faster than in (R+/-) animals. An equivalent desensitization resulted by exposing WT retinas to a background light producing 82 photoisomerizations rod(-1) sec(-1), suggesting that G90D rods in darkness act as if they are partially "light-adapted." Adding a second G90D allele gave (G+/+, R+/-) animals that exhibited a further increase of equivalent background light level but had no rod cell loss by 24 weeks of age. (G+/+, R-/-) retinas that express only the mutant rhodopsin develop normal rod outer segments and show minimal rod cell loss even at 1 year of age. We conclude that G90D is constitutively active in mouse rods in vivo but that it does not cause significant rod degeneration. Instead, G90D desensitizes rods by a process equivalent to light adaptation.

Adaptation, Ocular↗
PubMed1989

Four cone types characterized by anti-visual pigment antibodies in the pigeon retina.

Using three antibodies to visual pigments (monoclonal antibodies COS-1 and OS-2, and a polyclonal anti-opsin serum), four different types of cone cells could be distinguished in the red area (dorsoposterior part with the highest density of cones) of the pigeon retina. Both members of the double cone and the single cone with the red oil droplet were labelled with our monoclonal antibody COS-1 (type I cone). The single cone with the orange oil droplet was positive both with anti-opsin and monoclonal antibody OS-2 (type II cone). The single cone exhibiting a yellowish-green oil droplet, fluorescent in ultraviolet light, also reacted with anti-opsin but lacked the antigenic determinant recognized by OS-2 (type III cone). The thin cone with the small colorless oil droplet was negative with both COS-1 and anti-rhodopsin (type IV cone). We propose that the four immunologically distinguishable cone types correspond to cones expressing visual pigments with different (long-, middle-, short-wavelength and ultraviolet) color sensitivities.

Animals↗
PubMed1987

Surface glycoconjugates on rat photoreceptor cilium. Effect of neuraminidase digestion.

In retinal photoreceptors the connecting cilium constitutes a boundary between the inner and outer segments. In previous studies we demonstrated that, while opsin could be localized in abundance in the distal ciliary membrane, very little opsin was detected in the proximal ciliary plasma membrane. In the present study we extended our view of molecular specialization on the ciliary membrane with respect to glycoconjugates. Saccharide moieties of ciliary glycoconjugates were studied in immature and mature rat photoreceptors. Surface saccharides were detected and localized by means of ferritin-labeled lectins and electron microscopy. Dense labeling of the ciliary membrane surface with wheat germ agglutinin (WGA) was observed. In immature photoreceptors the labeling was restricted to the proximal ciliary membrane, in a region where opsin molecules could not be detected. Neuraminidase digestion abolished WGA binding to the proximal ciliary membrane surface, indicating that sialic acids mediate WGA binding to this domain. Peanut agglutinin (PNA) did not label the ciliary surface, nor did it bind to the surface of other photoreceptor domains. Neuraminidase digestion exposed numerous PNA binding sites on the ciliary membrane surface. In view of the carbohydrate specificity of PNA, we suggest that a terminal trisaccharide sequence, sialic acid-galactose-(beta 1----3)-N-acetyl galactosamine, is present in high density on the proximal ciliary membrane surface.

Animals↗
PubMed1986

Tunicamycin-induced dysgenesis of retinal rod outer segment membranes. II. Quantitative freeze-fracture analysis.

Tunicamycin (TM), a selective inhibitor of dolichylphosphate-dependent oligosaccharide biosynthesis, effectively blocks glycosylation, but not synthesis, of opsin, the rod visual pigment apoglycoprotein. In parallel with this inhibition, vesicular membrane material accumulates in the compartment between rod inner and outer segments (the intersegmental space) in TM-treated retinas (Fliesler et al, J Cell Biol 100:574-587, 1985). Freeze-fracture analysis was applied to isolated Xenopus laevis retinas which were incubated in the presence or absence of TM in order to clarify the relationship of those intersegmental membranous structures to others in the rod outer segment (ROS) assembly pathway. The membranes in the intersegmental space display characteristics similar to those of the ROS, but distinct from those of the inner segment. They exhibit densely particulate convex protoplasmic face (PF)-leaflets and relatively particle-free concave exoplasmic face (EF)-leaflets, similar to comparable leaflets of the ROS plasmalemma and nascent (immature) disc membranes. Quantitative analysis further demonstrates that the size distribution and densities of intramembrane particles (IMPs) in PF-leaflets of the intersegmental membranes are indistinguishable from those of ROS membranes, suggesting that both membrane systems contain similar integral proteins (i.e., opsin). Finally, the topology of the intersegmental membranes is most closely related to that of the ROS plasmalemma or nascent disc membranes, suggesting that they arise as a result of aberrant disc morphogenesis, rather than by breakdown of mature discs. Overall, the data support the conclusion that the tubulo-vesicular membranes in the intersegmental space represent newly assembled, opsin-containing material which has been efficiently compartmentalized in preparation for disc morphogenesis, but is incapable of forming normal, topologically closed discs.

Animals↗
PubMed1979

Structural and biochemical changes in vitamin A--deficient rat retinas.

The levels of rhodopsin and opsin were investigated in relation to the maintenance of retinal structure in retinas of vitamin A--deficient rats in low levels of cyclic illumination (1.5 to 2 foot-candles). Rhodopsin levels decreased in the deficient retinas to approximately 20% of control at 9 weeks, and this level was retained through 39 weeks on the deficient diet. Opsin levels decreased at a slower rate but reached about 20% of control levels at 32 weeks. Despite the decrease in rhodopsin levels, obvious deterioration of disc structure was not observed until 16 weeks of deficiency, when opsin levels had already decreased to 60% to 70% of control. The structural disruption of photoreceptor outer segments was localized initially in discs of the distal third. Rod cell degeneration preceded cone cell degeneration in vitamin A--deficient retinas. Most of the rods and cones persisted in the posterior retina at 23 weeks on the deficient diet; however, by 40 weeks, only 11% of the rod nuclei remained. In contrast, about 63% of the cone nuclei were present at 40 weeks of deficiency. The photoreceptor cells were affected by the deficiency to a greater extent in the inferior hemisphere than in the superior hemisphere of the eye.

Animals↗
PubMed1979

11-cis-Retinal-binding protein from bovine retina. Isolation and partial characterization.

11-cis-Retinal-binding protein from bovine retina has been purified to apparent homogeneity by gel filtration ion exchange, and hydroxylapatite chromatography. The molecular weight determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 33,000. A value of 36,000 was obtained by gel filtration. With 11-cis-retinal bound to the protein a bleachable spectral peak with maximum absorption at 425 nm was observed. When isolated without addition of exogenous retinal the purified binding protein displayed absorbance maxima at 340 and 425 nm, indicating the occurrence of two ligands in addition to the typical protein absorbance. The endogenous ligands responsible for these maxima were tentatively identified as 11-cis-retinol and 11-cis-retinal, respectively. The binding protein did not cross-react with antibodies prepared against bovine opsin, and its amino acid composition was distinct from that of opsin. The amount of retinal-binding protein extracted was approximately 1 nmol/retina or 1 mol of binding protein/20 mol of opsin. Its specificity and relative abundance suggest that the 11-cis-retinal-binding protein may play a major role in the visual cycle.

Amino Acids↗
PubMed1978

[Some features of rhodopsin regeneration process in the presence of exogenous 11Z-retinal in teleosts].

The rate of rhodopsin regeneration in decolorized rod outer segments ROS of pollock and ruff in the presence of exogenous 11Z-retinal is found to depend slightly on the temperature. The Arrhenius curve is linear within 0--20 degrees C and 0--30 degrees C in case of pollock and black ruff ROS respectively. The increase of the regeneration temperature above the upper limit results in both cases in the decrease of the chromophore binding rate due to the temperature denaturation of fish opsin. The rate of opsin regeneration in bovine ROS is temperature-dependent within 0--50 degrees C, the Arrhenius curves having a specific break with the temperature conversion at 12--13 degrees, which indicates a different 11Z-retinal binding rate with bovine opsin at low and high temperatures. Maximal rhodopsin regeneration temperature was observed within 5--10 min. for fish ROS and 1.5 hour for bovine ROS. Trimethylcyclohexene derivatives with a side chain of about 7 carbon atoms and 13Z-retinal competitively inhibited the rhodopsin regeneration in pollock and bovine ROS, while 13E-11, 12-dehydroretinal and all-E-retinal did not effect this process. Some peculiarities of the rhodopsin regeneration process in fish are discussed in connection with the molecular organization of a lipid phase of photoreceptor membrane and chromophore-binding region.

Animals↗
PubMed1994

Expression of retina-specific genes by mouse retinoblastoma cells.

PURPOSE: Two cell lines derived from ocular tumors of a transgenic mouse expressing the SV40 large T antigen have been established as models of human retinoblastoma. One line, TM, originated from a metastasis, and the other, TE, originated from the primary tumor. The authors compared these two lines with the normal adult mouse eye by analysis of the expression of five photoreceptor cell-specific proteins: IRBP, opsin, rod- and cone-specific transducins, and S-antigen. The authors sought to determine which of these proteins was expressed qualitatively and to examine semi-quantitatively for changes in the levels of expression in the cell lines. METHOD: Western blot analysis was used to detect photoreceptor-specific intracellular or secreted proteins. Total RNA was prepared from cultured cells or from mouse adult whole eye. Specific messenger levels in total RNA were determined either by northern hybridization analysis or by a semi-quantitative polymerase chain reaction (PCR), coupled to complementary DNA (cDNA) substrates prepared from total RNA. RESULTS: IRBP was present in the retinoblastoma cell lines and secreted into the medium. Neither S-antigen nor opsin were detectable by immunoblotting. IRBP and cone transducin mRNA were present in both cell lines. In contrast, opsin, rod transducin, and S-Antigen mRNAs were not detectable by PCR. beta-actin was present in the mRNA populations of whole eye and retinoblastoma. SV40 large T antigen mRNA was present only in retinoblastoma cells. CONCLUSIONS: IRBP and cone transducin expression in mouse retinoblastoma cells is independent of signaling provided directly or indirectly through large T antigen or Rb105 regulatory cascades. The pattern of photoreceptor-specific gene expression is similar to that seen in human retinoblastoma cell lines. These murine-derived cell lines may be useful as a tool to study IRBP and cone transducin expression in vitro and to determine early retinoblast expression patterns in the mouse.

Animals↗
PubMed2025

Rapid Divergence of Visual Systems and Signaling Traits to Contrasting Light Regimes During Early Speciation of African Crater Lake Cichlid Fish.

Sensory adaptation is widely hypothesized to drive ecological speciation, yet empirical evidence from natural populations undergoing early stage divergence remains limited. In Lake Masoko, a young crater lake in East Africa, the haplochromine cichlid Astatotilapia calliptera is undergoing early stage sympatric speciation into shallow-water littoral and deep-water benthic ecotypes that experience contrasting light environments. Here, we integrate retinal transcriptomics, phenotypic analyses, and visual modeling to uncover rapid sensory divergence associated with this ecological transition. We find striking shifts in cone opsin expression, with the benthic ecotype exhibiting a switch from short-wavelength sensitive SWS2B to SWS2A and an overall narrowing of cone sensitivity toward the center of the light spectrum, consistent with changes in deep-water light environment. In contrast, coding sequence variation in opsin genes was limited and no significant differences in allele frequencies were detected across nine polymorphic sites, pointing to expression regulation as the primary axis of early divergence in visual systems. In parallel, we observed divergence in male signaling traits, with benthic males displaying deeper red egg-spots, aligning with predictions from visual modeling of signal efficiency in different light environments. These results demonstrate rapid transcriptomic and phenotypic divergence in associated signaling traits-within ∼1,000 years-supporting a potential role for regulatory evolution in sensory adaptation during early ecological speciation.

Animals↗
PubMed1998

Histopathologic and immunohistochemical study of an autopsy eye with X-linked cone degeneration.

We performed a histopathologic and immunohistochemical study of eyes obtained at autopsy of an 84-year-old man from a family with X-linked cone degeneration in which affected members have a 6.5-kilobase deletion in the red cone pigment gene. At his most recent ocular examination, at age 71 years, this patient had had a visual acuity of 20/200 OU, fundus changes suggestive of macular degeneration, borderline-normal full-field rod electroretinograms, and profoundly reduced full-field cone electroretinograms. Histopathologic examination demonstrated marked loss of cone and rod photoreceptors and the retinal pigment epithelium in the central macula. The peripheral cone population was reduced, while the peripheral rod population was relatively preserved. Immunohistochemical examination with an antibody to both red and green cone opsin and an antibody to blue cone opsin disclosed a prominent loss of the red and green cone population and preservation of the blue cone population. These findings show that a defect in the red cone pigment gene can result in extensive degeneration of the red and green cone population across the retina.

Aged↗
PubMed1999

Photoreceptor rosettes in autosomal dominant retinitis pigmentosa with reduced penetrance.

We performed histopathologic and immunofluorescence studies of autopsy eyes from a 73-year-old woman with autosomal dominant retinitis pigmentosa from a family with reduced penetrance. Light microscopic examination showed extensive photoreceptor loss in most regions. In the temporal midperiphery of the retina, there were patches of remaining photoreceptors, some arranged in rosettes. Electron microscopic examination showed that these rosettes were composed mostly of rods, with a few cone-like inner segments. The malformed photoreceptor elements in the rosette lumens stained positively with anti-rhodopsin, but not with anti-red- and green-cone opsin or anti-blue-cone opsin. To our knowledge, this is the first report of photoreceptor rosettes containing rod photoreceptors in a case of retinitis pigmentosa. Future studies of additional patients will be needed to determine if the rod-abundant rosettes seen in our patient are a characteristic finding of autosomal dominant retinitis pigmentosa with reduced penetrance.

Aged↗