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Russell G Foster

Publications and source records attributed to Russell G Foster.

32 records · Page 2Linked to original sources
PubMed2003

In silico characterisation and chromosomal localisation of human RRH (peropsin)--implications for opsin evolution.

BACKGROUND: The vertebrate opsins are proteins which utilise a retinaldehyde chromophore in their photosensory or photoisomerase roles in the visual/irradiance detection cycle. The majority of the opsins, such as rod and cone opsins, have a very highly conserved gene structure suggesting a common lineage. Exceptions to this are RGR-opsin and melanopsin, whose genes have very different intron insertion positions. The gene structure of another opsin, peropsin (retinal pigment epithelium-derived rhodopsin homologue, RRH) is unknown. RESULTS: By in silico analysis of the GenBank database we have determined that the human RRH comprises 7 exons spanning approximately 16.5 kb and is localised to chromosome 4q25 in the following gene sequence: cen-EGF-RRH-IF-qter - a position that excludes this gene as a candidate for the RP29 autosomal recessive retinitis pigmentosa locus. A comparison of opsin gene structures reveals that RRH and RGR share two common intron (introns 1 and 4) insertion positions which may reflect a shared ancestral gene. CONCLUSION: The opsins comprise a diverse group of genes which appear to have arisen from three different lineages. These lineages comprise the "classical opsin superfamily" which includes the rod and cone opsins, pinopsin, VA-opsin, parapinopsin and encephalopsin; the RRH and RGR group; and the melanopsin line. A common lineage for RRH and RGR, together with their sites of expression in the RPE, indicates that peropsin may act as a retinal isomerase.

Amino Acid Sequence↗
PubMed2003

Expression of opsin genes early in ocular development of humans and mice.

We have compared the onsets of expression of the classical visual opsins with those of the non-rod, non-cone opsins in foetal and post-natal eye tissue from mice and humans. Mouse Rgr-opsin, peropsin, encephalopsin and melanopsin are all expressed in foetal development by E11.5, unlike the murine rod and cone opsins that exhibit post-natal expression, e.g. P1 for ultraviolet cone opsin and P5 for rod opsin. Human non-rod, non-cone opsins are also all expressed early, by 8.6 weeks post-conception. The implications of these observations are discussed with regard to the possible functions of these opsins at early stages of ocular development.

Animals↗
PubMed2003

A green cone-like pigment in the 'blind' mole-rat Spalax ehrenbergi: functional expression and photochemical characterization.

The degenerate subcutaneous eye of the blind mole rat belonging to the Spalax ehrenbergi superspecies has been shown to contain a long wavelength sensitive (LWS) cone pigment. Baculovirus expression of this LWS pigment and subsequent IMAC purification yields a photosensitive protein, that according to absorbance maximum (530 +/- 2 nm), kinetics of late phototransitions, and transducin activation, has all characteristics of a functional green cone pigment. The absorbance spectrum of the Spalax pigment is strongly red-shifted relative to the very homologous mouse, rabbit and rat green cone pigments (508-510 nm). Also in contrast to the rodent pigments, the Spalax pigment exhibits anion-dependent spectral properties, displaying a 12 nm blue-shift upon substitution of chloride ions by nitrate ions. Finally, the slow part of the photocascade deviates in some aspects from that of sighted mammals. The possible relevance of these findings for the evolutionary adaptation of Spalax to a subterranean ecotope is discussed.

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PubMed2003

Melanopsin retinal ganglion cells and the maintenance of circadian and pupillary responses to light in aged rodless/coneless (rd/rd cl) mice.

Melanopsin-expressing ganglion cells have been proposed as the photoreceptors mediating non-rod, non-cone ocular responses to light. Here we use the aged (approximately 2 years) rodless and coneless (rd/rd cl) mouse to assess the impact of progressive inner retinal cell loss on melanopsin expression, circadian entrainment and pupillary constriction. Aged rd/rd cl mice show substantial transneuronal retinal degeneration leaving only the ganglion cell layer and little of the inner nuclear layer. Despite this loss, quantitative reverse transcriptase-polymerase chain reaction showed normal levels of melanopsin expression, and immunocytochemistry demonstrated both the presence and normal cellular appearance of these cells. Furthermore, the optic nerves of the two genotypes (rd/rd cl and +/+) were not obviously different in animals older than 2 years. However, this massive level of retinal degeneration left both pupillary and circadian responses to light intact, even in rd/rd cl mice older than 2 years. Our data provide the first positive correlation between the persistence of melanopsin-expressing cells and the maintenance of both circadian and pupillary responses to light in the absence of rods and cones. These findings, together with recent studies on melanopsin knockout mice, are consistent with the hypothesis that melanopsin-expressing ganglion cells are photosensitive and mediate a range of irradiance-detection tasks.

Aging↗
PubMed2003

Light-induced c-fos in melanopsin retinal ganglion cells of young and aged rodless/coneless (rd/rd cl) mice.

Non-rod, non-cone ocular photoreceptors have been shown to mediate a range of irradiance detection tasks. The strongest candidates for these receptors are melanopsin-positive retinal ganglion cells (RGCs). To provide a more complete understanding of these receptors in vivo, we have utilized a mouse that lacks rod and cone photoreceptors (rd/rd cl) and compared these animals to congenic wild-types. Using real-time polymerase chain reaction and immunohistochemistry, we address the following. (1) Is Fos expression within these RGCs driven by an input from the rods/cones or is it the product of the intrinsic photosensitivity of these neurons? We demonstrate that most Fos expression across the entire retina is due to the rods/cones, but in the absence of these photoreceptors, light will induce Fos within melanopsin RGCs. (2) Could the reported age-related decline in circadian photosensitivity of rodents be linked to changes in the population of melanopsin RGCs? We show that old mice experience an approximately 40% reduction in melanopsin RGCs. (3) Does the loss of inner retinal neurons affect the responses of melanopsin RGCs? Aged (approximately 700 days) rd/rd cl mice lose most of their inner retina but retain the retinal ganglion cell layer. In these mice, the proportion of melanopsin RGCs that express Fos in response to light is significantly reduced. Collectively, our data suggest that melanopsin RGCs form a heterogeneous population of neurons, and that most of the light-induced c-fos expression within these cells is associated with the endogenous photosensitivity of these neurons.

Aging↗
PubMed2003

Non-rod, non-cone photoreception in rodents and teleost fish.

Until recently, all ocular photoreception was attributed to the rods and cones of the retina. However, studies on mice lacking rod and cone photoreceptors (rd/rd cl), has shown that these mice can still use their eyes to detect light to regulate their circadian rhythms, suppress pineal melatonin, modify locomotor activity and modulate pupil size. In addition, action spectra for some of these responses have characterized a novel opsin/vitamin A-based photopigment with a lambda(max) approximately 480 nm. Electrophysiological studies have shown that a subset of retinal ganglion cells are intrinsically photosensitive, and melanopsin has been proposed as the photopigment mediating these responses to light. In contrast to mammals, an inner retinal photopigment gene has been identified in teleost fish. Vertebrate ancient (VA) opsin forms a photopigment with a lambda(max) between 460-500 nm, and is expressed in a sub-set of retinal horizontal cells, and cells in the amacrine and ganglion cell layers. Electrophysiological analysis suggests that VA opsin horizontal cells are intrinsically photosensitive and encode irradiance information. In contrast to mammals, however, the function of these novel ocular photoreceptors remains unknown. We compare non-rod, non-cone ocular photoreceptors in mammals and fish, and examine the criteria used to place candidate photopigment molecules into a functional context.

Amino Acid Sequence↗
PubMed2002

Zebrafish melanopsin: isolation, tissue localisation and phylogenetic position.

Photoreception is best understood in retinal rods and cones, but it is not confined to these cells. In non-mammals, intrinsically photosensitive cells have been identified within several structures including the pineal, hypothalamus and skin. More recently novel light sensitive cells have been identified in the inner/basal retina of both teleosts and rodents. Melanopsin has been proposed as the photopigment mediating many of these non-rod, non-cone responses to light. However, much about the melanopsin gene family remains to be clarified including their potential role as photopigments, and taxonomic distribution. We have isolated the first orthologue of melanopsin from a teleost fish and show expression of this gene in a sub-set of retinal horizontal cells (type B). Zebrafish melanopsin, and orthologues of this gene, differ markedly from the vertebrate photopigment opsins. The putative counterion is not a glutamate but a tyrosine, the putative G-protein binding domain in the third cytoplasmic loop is not conserved, and they show low levels of amino acid identity (approximately 27%) to both the known photopigment opsins and to other members of the melanopsin family. Mouse melanopsin is only 58% identical to Xenopus, and 68% identical to zebrafish. By contrast, the photosensory opsin families show approximately 75% conservation. On the basis of their structure, genomic organisation, discrete evolutionary lineage, and their co-expression with other opsins, the melanopins are not obvious photosensory opsins. They might represent a separate branch of photopigment evolution in the vertebrates or they may have a non-direct photosensory function, perhaps as a photoisomerase, in non-rod, non-cone light detection.

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PubMed2002

Opsins and mammalian photoentrainment.

Research over the past decade has provided overwhelming evidence that photoreception in the vertebrate eye is not confined to the rod and cone photoreceptors. It appears that photoreceptor cells within the inner retina provide irradiance information to a wide variety of different photosensory tasks including photoentrainment, pupillary constriction and masking behaviour. Action spectra in mice lacking all rod and cone photoreceptors ( rd/rd cl) have demonstrated the existence of a previously uncharacterised, opsin/vitamin-A-based photopigment with peak sensitivity at 479 nm (opsin photopigment/OP(479)). The review addresses the question: has the gene encoding OP(479) already been isolated, and if not, what type of gene should we be seeking and where in the eye might this gene be expressed? On the basis of available data, the gene that encodes OP(479) remains unidentified, and two broad possibilities exist. On the assumption that OP(479) will be like all of the other vertebrate photopigments (ocular and extraocular) and share a close phylogenetic relationship based upon amino acid identity and a conserved genomic structure, then the gene encoding OP(479) has yet to be isolated. Alternatively, there may have been a separate line of photopigment evolution in the vertebrates that has given rise to the melanopsin family. If true then the mammalian melanopsin gene may encode OP(479). Only when melanopsin and other candidates for OP(479) have been functionally expressed, and shown to encode a photopigment that matches the action spectrum of OP(479), can firm conclusions about the identity of the non-rod, non-cone ocular photoreceptor of mammals be made.

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PubMed2002

Placing ocular mutants into a functional context: a chronobiological approach.

The behavior of mammals is characterized by a 24-h cycle of rest and activity which is a fundamental adaption to the solar cycle of light and darkness. The pacemaker of this circadian clock is localized in the ventral part of the hypothalamus, the so-called suprachiasmatic nuclei (SCN), and is entrained by light signals mediated by the eye. The eye is directly connected via the retinohypothalamic tract (RHT) to the SCN. Light that reaches the retina elicits glutamate release at the synaptic terminals of the RHT and influences the neurons in the SCN in a manner that alters the behavioral state of the animal. A light pulse that reaches the retina at the beginning of the night elicits a delay of the clock phase, whereas a light pulse that reaches the retina at the end of the dark period leads to an advance of the clock phase. This advance or delay can be quantified by measuring the change in onset of wheel-running activity. Such measurements have, and continue to provide, a remarkably powerful assay of how light is detected and transduced to regulate circadian rhythms. The methods used for such measurements in mice are described in the following article.

Animals↗
PubMed2002

Non-rod, non-cone photoreception in the vertebrates.

When reflected from a surface, light can provide a representation of the spatial environment, whilst gross changes in environment light can signal the time of day. The differing sensory demands of using light to detect environmental space and time appear to have provided the selection pressures for the evolution of different photoreceptor systems in the vertebrates, and probably all animals. This point has been well recognised in the non-mammals, which possess multiple opsin/vitamin A-based photoreceptor populations in a variety of sites distributed both within and outside the CNS. By contrast, eye loss in mammals abolishes all responses to light, and as a result, all photoreception was attributed to the rods and cones of the retina. However, studies over the past decade have provided overwhelming evidence that the mammalian eye contains a novel photoreceptor system that does not depend upon the input from the rods and cones. Mice with eyes but lacking rod and cone photoreceptors can still detect light to regulate their circadian rhythms, suppress pineal melatonin, modify locomotor activity, and modulate pupil size. Furthermore, action spectra for some of these responses in rodents and humans have characterised at least one novel opsin/vitamin A-based photopigment, and molecular studies have identified a number of candidate genes for this photopigment. Parallel studies in fish showing that VA opsin photopigment is expressed within sub-sets of inner retina neurones, demonstrates that mammals are not alone in having inner retinal photoreceptors. It therefore seems likely that inner retinal photoreception will be a feature of all vertebrates. Current studies are directed towards an understanding of their mechanisms, determining the extent to which they contribute to physiology and behaviour in general, and establishing how they may interact with other photoreceptors, including the rods and cones. Progress on each of these topics is moving very rapidly. As a result, we hope this review will serve as an introduction to the cascade of papers that will emerge on these topics in the next few years. We also hope to convince the more casual reader that there is much more to vertebrate photoreceptors than the study of retinal rods and cones.

Animals↗
PubMed2002

Visual pigments and oil droplets in diurnal lizards: a comparative study of Caribbean anoles.

We report microspectrophotometric (MSP) data for the visual pigments and oil droplets of 17 species of Caribbean anoline lizard known to live in differing photic habitats and having distinctly different dewlap colors. The outgroup Polychrus marmoratus was also examined to gain insight into the ancestral condition. Except for Anolis carolinensis, which is known to use vitamin A(2) as its visual pigment chromophore, all anoline species examined possessed at least four vitamin-A(1)-based visual pigments with maximum absorbance (lambda(max)) at 564, 495, 455 and 365 nm. To the previously reported visual pigments for A. carolinensis we add an ultraviolet-sensitive one with lambda(max) at 365 nm. Five common classes of oil droplet were measured, named according to apparent color and associated with specific cone classes - yellow and green in long-wavelength-sensitive (LWS) cones, green only in medium-wavelength-sensitive (MWS) cones and colorless in short-wavelength-sensitive (SWS) and ultraviolet-sensitive (UVS) cones. MSP data showed that the colorless droplet in the SWS cone had significant absorption between 350 and 400 nm, while the colorless droplet in the UVS cone did not. The pattern for Polychrus marmoratus was identical to that for the anoles except for the presence of a previously undescribed visual cell with a rod-like outer segment, a visual pigment with a lambda(max) of 497 nm and a colorless oil droplet like that in the UVS cones. These findings suggest that anoline visual pigments, as far as they determine visual system spectral sensitivity, are not necessarily adapted to the photic environment or to the color of significant visual targets (e.g. dewlaps).

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PubMedDate not supplied

Residual photosensitivity in mice lacking both rod opsin and cone photoreceptor cyclic nucleotide gated channel 3 alpha subunit.

The mammalian retina contains three classes of photoreceptor. In addition to the rods and cones, a subset of retinal ganglion cells that express the putative sensory photopigment melanopsin are intrinsically photosensitive. Functional and anatomical studies suggest that these inner retinal photoreceptors provide light information for a number of non-image-forming light responses including photoentrainment of the circadian clock and the pupil light reflex. Here, we employ a newly developed mouse model bearing lesions of both rod and cone phototransduction cascades (Rho(-/-) Cnga3(-/-)) to further examine the function of these non-rod non-cone photoreceptors. Calcium imaging confirms the presence of inner retinal photoreceptors in Rho(-/-) Cnga3(-/-) mice. Moreover, these animals retain a pupil light reflex, photoentrainment, and light induction of the immediate early gene c-fos in the suprachiasmatic nuclei, consistent with previous findings that pupillary and circadian responses can employ inner retinal photoreceptors. Rho(-/-) Cnga3(-/-) mice also show a light-dependent increase in the number of FOS-positive cells in both the ganglion cell and (particularly) inner nuclear layers of the retina. The average number of cells affected is several times greater than the number of melanopsin-positive cells in the mouse retina, suggesting functional intercellular connections from these inner retinal photoreceptors within the retina. Finally, however, while we show that wild types exhibit an increase in heart rate upon light exposure, this response is absent in Rho(-/-) Cnga3(-/-) mice. Thus, it seems that non-rod non-cone photoreceptors can drive many, but not all, non-image-forming light responses.

Animals↗
PubMedDate not supplied

Melanopsin (Opn4) positive cells in the cat retina are randomly distributed across the ganglion cell layer.

A rare type of rodent retinal ganglion cell expresses melanopsin (Opn4), the majority of which project to the suprachiasmatic nuclei. Many of these cells are directly light sensitive and appear to regulate the circadian system in the absence of rod and cone photoreceptors. However, the rodent retina contains no overt regions of specialization, and the different ganglion cell types are hard to distinguish. Consequently, attempts to distinguish the distribution of melanopsin ganglion cells in relation to regions of retinal specialization or subtype have proved problematic. Retinal cells with a common function tend to be regularly distributed. In this study, we isolate cat melanopsin and label melanopsin expressing cells using in situ hybridization. The labelled cells were all confined to the ganglion cell layer, their density was low, and their distribution was random. Melanopsin containing cells showed no clear center-to-periphery gradient in their distribution and were comprised of a relatively uniform cellular population.

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