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Visual pigments in the early life stages of Pacific northwest marine fishes.

Microspectrophotometry was used to measure the visual pigments in the rods and cones of 22 species of marine fish larvae netted from the surface waters off Friday Harbor Laboratories, Washington, USA. 13 species had rods, 12 of which contained visual pigments with a wavelength of maximum absorbance near 500 nm, while one, the sand lance (Ammodytes hexapterus), had its absorbance maximum at 482 nm. The 22 species of fish larvae possessed varied combinations of single, double and twin cones, ranging in peak absorbance from 353 nm to 584 nm. Of these, green-sensitive single cones were present in 20 of the 22 species, and were the dominant cone type. Double and twin cones were present in 13 of the species. Most common were identical green-sensitive (twin) cones (in 11 species). Green/yellow-sensitive double cones occurred in four species. In a single instance (Hemilepidotus hemilepidotus) twin blue-sensitive, twin green-sensitive and double blue/yellow-sensitive cones were recorded. Of particular interest was the finding that 18 of the species had ultraviolet- and/or violet-absorbing single cones. It has been suggested that short-wavelength photosensitivity may be beneficial for planktivory by extending the spectral range over which vision can occur. The high percentage (82%) of ultraviolet and violet visual pigments in Pacific northwest fish larvae supports the prediction that short-wavelength sensitivity may be common in marine fish larvae.

Aging↗

Evidence supportive of a functional discrimination between photopic oscillatory potentials as revealed with cone and rod mediated retinopathies.

We report on a family where four of the eleven children presented with reduced visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test, normal appearing fundi and unexpected electroretinographic findings. Light- (photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory potentials (OPs) were obtained following an accepted standard protocol. The b-wave of their photopic ERG was significantly more attenuated than the a-wave due to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within the normal range, giving to the b-wave a truncated appearance reminiscent of that seen in congenital stationary night blindness (CSNB) with myopia. Interestingly in the latter condition, which is believed to result from an ON-retinal pathway anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of normal amplitude thus resulting in an OP response pattern which complements that seen with our patients. Also of interest is the fact that, in our patients, the amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured in light-adaptation while, in normal, a non-significant 14% increase is noted; a finding which is in keeping with other studies reporting supernormal scotopic ERGs in some forms of cone dystrophies. Based on the photopic OP response pattern, our patients represent the electrophysiological complement of patients affected with CSNB. Interestingly their symptoms are also complementary, a finding which could support a functional discrimination between the photopic OPs.

Adolescent↗

Progressive cone dystrophy with deutan genotype and phenotype.

PURPOSE: To study the electroretinographic signals originating in the long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cone pathways by means of large-field and multifocal cone type-specific electroretinograms (ERGs) in a patient with progressive cone dystrophy. METHODS: A 65-year-old male patient with colour vision disturbances (age at onset 10 years), loss of visual acuity (14 years), and central visual field defects (40 years) was investigated. Large-field flicker-ERG responses to stimuli that exclusively modulated the L-cones or the M-cones, or the two simultaneously (both in-phase and in counter-phase), were measured. Short-wavelength-sensitive (S) cones were not modulated. Multifocal ERGs (mfERGs) were also recorded, with a pattern-reversing display that modulated only the L- or the M-cones at equal cone contrasts and average quantal catches. Genetic analysis of L- and M-pigment genes was performed on genomic DNA isolated from peripheral venous blood. RESULTS: The patient showed a normal rod-driven ERG but reduced cone-driven electroretinographic amplitudes with normal implicit times in the International Society for Clinical Electrophysiology of Vision (ISCEV) standard ERG. The large-field flicker-ERG responses to pure L-cone modulation were significantly above noise level but were substantially reduced in comparison with both normal trichromatic subjects and (otherwise normal) deuteranopes. The L-cone driven electroretinographic implicit times and phases were within normal limits. The M-cone driven electroretinographic responses were not detectable. A model fit of all the L- and M-cone driven flicker-ERG data revealed that the responses were exclusively driven by the L-cones. Consistently, the cone type-specific mfERGs showed severely reduced but detectable responses to L-cone-isolating stimuli. The M-cone driven multifocal-ERG responses were undistinguishable from noise. The L- and M-pigment gene array consisted of only a single L-pigment gene. The complete coding sequence of this gene was determined and showed no abnormality. CONCLUSIONS: This patient exhibits a coincidence of progressive cone dystrophy and deuteranopia. The molecular genetic data of the L/M-pigment gene array is consistent with the deutan phenotype. It cannot be excluded that the rearrangement of the X-chromosome pigment gene array is responsible for the cone dystrophy in this patient. It is, however, suggested that the dichromacy and the cone dystrophy have different and independent genetic origins.

Aged↗

Differential localization and expression of alpha and beta isoenzymes of protein kinase C in the rat retina.

Expression and cellular localization of three isoenzymes of Ca2+-dependent protein kinase C (PKCalpha, PKCbeta, and PKCgamma) in the adult rat retina were revealed by immunohistochemistry and in situ hybridization histochemistry with isoenzyme-specific antibodies and cRNA probes. Immunoreactivities and mRNA signals for PKCalpha were conspicuous in rod bipolar cells. A subgroup of amacrine cells expressed PKCalpha. The cells in the ganglion cell layer also displayed PKCalpha gene products. Positive immunoreactivities for PKCbeta were localized as stripe patterns in the inner plexiform layer, corresponding to the stratification levels of axon terminals of cone bipolar cells. The somata of cone bipolar cells expressed PKCbeta. Amacrine cells and retinal ganglion cells also displayed PKCbeta gene products. The results obtained by immunohistochemistry were confirmed with colocalization of mRNA signals for PKCalpha and PKCbeta on the somata. The cell membranes showed stronger immunoreactivities than did the cytoplasms for both PKCalpha and PKCbeta. Neither immunoreactivities nor mRNA signals for PKCgamma were detected in all retinal regions. The differential roles of Ca2+-dependent PKC isoenzymes could be revealed in physiological defined retinal neurons.

Animals↗

Neuronal coupling in the central nervous system: lessons from the retina.

The retina is a model system for studying gap junctional intercellular communication in the CNS. The cellular coupling can be graphically visualized in retinal whole mounts by injecting small cationic tracers into microscopically identified neurons; the pattern of tracer coupling shown by each type of retina neuron is highly stereotyped, with many types of amacrine cells and ganglion cells showing complex patterns of both homologous and heterologous coupling. Parallel physiological studies have demonstrated that the gap junctions can be modulated dynamically by neurotransmitters and by the level of ambient illumination. Taken together, the numerous structural and functional studies on gap junctions in the retina provide powerful support for the concept that electrical synapses are complex components of neuronal circuits, having many of the attributes normally ascribed to chemical synapses.

Animals↗

A leucine-rich repeat membrane protein, 5T4, is expressed by a subtype of granule cells with dendritic arbors in specific strata of the mouse olfactory bulb.

Segregation of neuron-type-specific synaptic connections in different strata is a characteristic feature shared by the olfactory bulb (OB) and retina. In the mammalian OB, mitral cells form dendrodendritic synapses with granule cells (GCs) in the deep stratum of the external plexiform layer (EPL), whereas tufted cells form dendrodendritic synapses in the superficial stratum. In the search for membrane proteins with strata-specific expression patterns, we found that a leucine-rich repeat membrane protein (5T4 oncofetal trophoblast glycoprotein) was expressed selectively by a subset of superficial GCs. The somata of 5T4-positive GCs were localized in or near the mitral cell layer, and their apical dendrites ramified preferentially in the superficial stratum of the EPL, where tufted cell dendrites ramified. Strata-specific expression of 5T4 was found also in the retina: 5T4 was expressed selectively by rod-bipolar cells and a subset of amacrine cells whose dendrites ramified in a specific sublamina of the inner plexiform layer. During the perinatal and postnatal development of the OB, 5T4 expression paralleled in time the formation of dendrodendritic synapses in the EPL. Odor deprivation during the first postnatal month selectively reduced the thickness of the superficial stratum of the EPL and the number of 5T4-positive GCs. Because 5T4 is known to interact with actin cytoskeleton, these observations suggest that 5T4 is involved in the formation or maintenance of strata-specific dendritic ramification or synaptic connection of subsets of local interneurons.

Amacrine Cells↗

AII amacrine cell population in the rabbit retina: identification by parvalbumin immunoreactivity.

Parvalbumin (PV) is a calcium-binding protein localized to selected neurons in the nervous system, including the retina. This investigation evaluated the distribution of PV immunoreactivity in the rabbit retina using immunohistochemistry with a monoclonal antibody directed to carp PV. In the inner nuclear layer (INL), PV immunoreactivity was present in horizontal and amacrine cells. In the ganglion cell layer, PV immunostaining was confined to somata that are likely to be both displaced amacrine cells and ganglion cells. PV-immunoreactive (IR) amacrine cells were positioned in the proximal INL adjacent to the inner plexiform layer (IPL). These cells usually gave rise to a single primary process, which arborized into two distinct bands in the IPL. In sublamina a, the processes were thin and had large, irregular endings. In sublamina b, multiple processes branched from the primary process and were characterized by varicosities and spines. PV-IR amacrine cell bodies measured from 8 to 10 microns in diameter. Their density was highest in the visual streak and lowest in the periphery of the superior retina. The average number of PV-IR amacrine cells was 464,045 cells per retina (N = 3), and the average regularity index of the PV-IR cell mosaic was 3.23. PV-IR amacrine cells were further characterized by double-label immunofluorescence experiments using antibodies to PV and tyrosine hydroxylase (TH). Varicose TH-IR processes were in close apposition to many PV-IR amacrine cells and often formed "ring structures" around them. Together, these morphological, quantitative, and histochemical observations indicate that PV immunoreactivity in the INL is localized predominantly to AII amacrine cells, and therefore it is a valuable marker for the identification of this cell type.

Animals↗

Eye defects in receptor protein-tyrosine phosphatase alpha knock-down zebrafish.

Receptor protein-tyrosine phosphatase alpha (RPTP alpha) is highly expressed in the developing retina of different species, but little is known about its function there. Here, we report that injection of antisense morpholinos in zebrafish embryos reduced RPTP alpha expression to almost nondetectable levels up to 3 days postfertilization (dpf). RPTP alpha was detectable again from 4 dpf onward. RPTP alpha knock-down resulted in smaller eyes. Examination of sections of the retina at different developmental stages demonstrated that already at 28 hours postfertilization (hpf) fewer cells were present in the retina of RPTP alpha-morpholino-injected embryos. At 3 dpf, the layered organization of the retina was absent. In addition, the morphology and labeling with an axon specific antibody, acetylated tubulin, demonstrated that most cells appeared to be undifferentiated. Strikingly, at 5 dpf the lamination of the retina was partially restored, concomitant with re-expression of RPTP alpha protein. Although cells in the retina were now differentiated, the layering of the retina remained disrupted and significant gaps were observed in the amacrine cell layer. Therefore, knock-down of RPTP alpha protein provides evidence that RPTP alpha is essential for normal retinal development.

Animals↗

Homozygous tandem duplication within the gene encoding the beta-subunit of rod phosphodiesterase as a cause for autosomal recessive retinitis pigmentosa.

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the rhodopsin and phosphodiesterase beta-subunit (PDEB) loci have been reported. To assess the involvement of PDEB in ARRP families from Spain, we screened a panel of 19 families for linkage to markers within or close to the PDEB gene. Homozygosity was also tested in cases of consanguinity. This combined approach ruled out PDEB as the cause of the disease in all but one of the families. Molecular characterization of the gene in that family (a consanguineous pedigree) revealed a homozygous 71-bp tandem duplication in exon 1 of the affected member, the parents being heterozygous. This defect causes a frameshift mutation which leads to a premature stop codon, suggesting that this mutant allele is the underlying cause of ARRP in this patient. According to the data presented here, the PDEB gene is not the main gene responsible for ARRP, but accounts for about 5% of the cases.

Base Sequence↗

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↗

Histopathological and immunocytochemical demonstration of retinal degeneration in the squirrel monkey.

Here we describe the spontaneous appearance of a retinal degeneration in two squirrel monkeys (New World monkey). Since the retinal pathology sufficiently resembles that seen in human degenerative disorder, studies of degeneration in monkeys could contribute to the prevention and treatment of the human disorder. The histopathological examination of horizontal sections comprising the optic disc and the fovea revealed photoreceptor outer and inner segments only in the central fovea. The morphology of the photoreceptors and outer nuclear layer changed rapidly away from the central fovea. There was a loss of outer segments, a shortening of inner segments and disorganized and flattened cells were found in the outer nuclear layer. AO labelling not only detected opsin in the few areas where outer segments were present, but also in the inner segments and the outer nuclear layer. The OS-2 antibody failed to stain the outer segments of the blue sensitive cones. The COS-1 antibody stained many red/green sensitive cones in the fovea, but their density decreased quickly outside this region. Thus, we have detected retinal degeneration in two outbred squirrel monkeys who were being examined for other reasons unrelated to research in retinal degeneration. One was feral and the other was only two generations removed from the feral state. The identification of retinal degeneration in a non-human primate holds great promise for the development of a treatment for human retinitis pigmentosa because access to a primate model would be of invaluable importance for studying the biochemistry behind these disorders.

Animals↗

Retinal degeneration in retinitis pigmentosa and neuronal ceroid lipofuscinosis: An overview.

Retinal degeneration is an early consequence of the group of lysosomal storage diseases collectively referred to as the neuronal ceroid lipofuscinoses (NCLs). This review details specialized techniques that have evolved for retinal assessment in patients with hereditary retinal degeneration. A standard ERG protocol is described for assessing rod- and cone-mediated function. Standardization will be crucial for planning and implementing multicenter trials as rational therapeutic intervention becomes available. In recent years, there has been a dramatic increase in knowledge of the molecular biological bases of retinitis pigmentosa and allied retinal degenerations. Rather than attempting a comprehensive summary, this review stresses the concepts of genetic, allelic, and clinical heterogeneity, which have obvious parallels in the NCLs. Many of the mutations that cause retinal degeneration are in genes that encode photoreceptor cascade proteins; others are in genes that encode photoreceptor structural proteins. Recent advances in linking the retinal degeneration slow (RDS) and ATP-binding cassette transporter retina (ABCR) genes to a variety of disease phenotypes will be summarized. Clinical heterogeneity even among family members with the same mutation raises the possibility that modifying factors, either genetic or environmental, could influence the severity of the disease. Here, we focus on vitamin A and docosahexaenoic acid, two potential nutritional modifiers that have received considerable attention in recent years.

Child↗

A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two RP sisters of a consanguineous family.

We report the molecular analysis of the beta subunit of the rod phosphodiesterase (PDEB) gene in a consanguineous autosomal recessive retinitis pigmentosa family that shows homozygosity for polymorphisms in the genomic region comprising this gene, and positive linkage between a PDEB marker and the disease. The two affected sisters are homozygous for a T to G transversion in codon 699 of the PDEB gene, leading to the substitution of a leucine by an arginine residue. This change, enclosed in the catalytic domain of the PDEB, could result in a modification of the protein structure preventing the physiological hydrolysis of cGMP.

3',5'-Cyclic-GMP Phosphodiesterases↗

Visual pigments and optical habitats of surfperch (Embiotocidae) in the California kelp forest.

We studied the optical microhabitat use and visual pigment variation among a group of closely related teleosts (surfperch: Embiotocidae) living along the nearshore central California coast. We employed a diver-operated spectroradiometer to record the optical microhabitat use of eight surfperch species in Monterey Bay. and microspectrophotometry to measure visual pigment absorbance for nine surfperch species. Species were dichromatic with mixtures of A1- and A2-based visual pigments exhibiting extensive maximum absorbance (lambda(max)) variation across species: 455-482 nm for SWS cones and 527-546 nm for LWS cones. Interspecific variation in sidewelling irradiance measurements (mean lambdaFmaxs) significantly accounted for 63% of the variation in surfperch LWS visual pigments and 83% of the interspecific variation in SWS visual pigments using a phylogenetically-corrected regression technique. Optimality models for maximizing relative photon capture of background radiance demonstrate that the LWS cone lambda(max) values are tuned for maximizing photon capture of the species-specific horizontal visual field, while the SWS cone lambda(max), are well offset from the dominant background radiance. This study is one of the first to demonstrate species-specific differences in habitat usage at microhabitat scales accounting for differences in photoreceptor peak absorbance among closely related, sympatric species.

Animals↗

Double-labeling techniques demonstrate that rod bipolar cells are under GABAergic control in the inner plexiform layer of the rat retina.

The synaptic connectivity between rod bipolar cells and GABAergic neurons in the inner plexiform layer (IPL) of the rat retina was studied using two immunocytochemical markers. Rod bipolar cells were stained with an antibody specific for protein kinase C (PKC, alpha isoenzyme), and GABAergic neurons were stained with an antiserum specific for glutamic-acid decarboxylase (GAD). Some amacrine cells were also labeled with the anti-PKC antiserum. All PKC-labeled amacrine cells examined showed GABA immunoreactivity, indicating that PKC-labeled amacrine cells constitute a subpopulation of GABAergic amacrine cells in the rat retina. A total of 150 ribbon synapses established by rod bipolar cells were observed in the IPL. One member of the postsynaptic dyads was always an unlabeled AII amacrine cell process, and the other belonged to an amacrine-cell process showing GAD immunoreactivity. The majority (n=92) (61.3%) of these processes made reciprocal synapses back to the axon terminals of rod bipolar cells. In addition, 78 conventional synapses onto rod bipolar axons were observed, and among them 52 (66.7%) were GAD-immunoreactive. Thus GABA provides the major inhibitory input to rod bipolar cells.

Animals↗

Optic nerve response and retinal structure in rainbow trout of different sizes.

This study presents evidence of ultraviolet (UV) sensitive, ON center ganglion cells in the fish retina. We determined the spectral sensitivity of ON and OFF responses from the optic nerve mass potential in small (18.0 - 28.5 g) and large (59.5-835 g) rainbow trout, with special reference to UV sensitivity. Under a mid+long-wavelength adapting background, the ON response of small fish revealed the presence of a UV cone mechanism (lambda max 390 nm) which was absent in large specimens. Under similar background conditions, the OFF response of both small and large fish showed one sensitivity peak, dominated by inputs from an M-cone mechanism. An almost complete absence of the accessory corner cones from the retinal mosaic was correlated with the loss of UV sensitivity.

Action Potentials↗