Amino acid sequence of the retinal binding site of squid visual pigment

The retinylpeptides of visual pigments of two species of squid were identified in invertebrate visual pigments. Their primary structures were identical: H-Phe-Ala-Lys-Ala-Ser-Ala-Ile-His-Asn-pro-Hse(Met)-OH. The sequence was homologous to those of the corresponding region of other visual pigments, but the eighth amino acid, His, was found in squid visual pigments. In this experiment the retinylpeptides of eleven amino acid residues were isolated by monitoring the absorbance spectrum of the reduced retinal Schiff base without using radio-active [3H]retinal. This method is valid for the isolation and identification of retinylpeptides of other invertebrate visual pigments in which the chromophore is not exchangeable.     

Autoradiographic analysis of retinal projections in the flatfish Scophthalmus maximus L

The organization of retinal projections were examined in the flatfish Scophthalmus maximus using the autoradiographic technique. Overall 15 different contralateral primary optic centers were identified at hypothalamic, thalamo-pretectal, tectal and tegmento-mesencephalic levels. A weak ipsilateral retinal contingent was also observed. Elsewhere, the retinal projections of the migrating eye in comparison to those of the non-migrating eye were observed to be similar.     

The effects of dietary carotenoid supplementation and retinal carotenoid accumulation on vision-mediated foraging in the house finch

Background

For many bird species, vision is the primary sensory modality used to locate and assess food items. The health and spectral sensitivities of the avian visual system are influenced by diet-derived carotenoid pigments that accumulate in the retina. Among wild House Finches (Carpodacus mexicanus), we have found that retinal carotenoid accumulation varies significantly among individuals and is related to dietary carotenoid intake. If diet-induced changes in retinal carotenoid accumulation alter spectral sensitivity, then they have the potential to affect visually mediated foraging performance.

Methodology/Principal Findings

In two experiments, we measured foraging performance of house finches with dietarily manipulated retinal carotenoid levels. We tested each bird''s ability to extract visually contrasting food items from a matrix of inedible distracters under high-contrast (full) and dimmer low-contrast (red-filtered) lighting conditions. In experiment one, zeaxanthin-supplemented birds had significantly increased retinal carotenoid levels, but declined in foraging performance in the high-contrast condition relative to astaxanthin-supplemented birds that showed no change in retinal carotenoid accumulation. In experiments one and two combined, we found that retinal carotenoid concentrations predicted relative foraging performance in the low- vs. high-contrast light conditions in a curvilinear pattern. Performance was positively correlated with retinal carotenoid accumulation among birds with low to medium levels of accumulation (∼0.5–1.5 µg/retina), but declined among birds with very high levels (>2.0 µg/retina).

Conclusion/Significance

Our results suggest that carotenoid-mediated spectral filtering enhances color discrimination, but that this improvement is traded off against a reduction in sensitivity that can compromise visual discrimination. Thus, retinal carotenoid levels may be optimized to meet the visual demands of specific behavioral tasks and light environments.     

The ultimobranchial gland of the dogfishScyliorhinus canicula L. immunofluorescence cross-reactivities with anti-sera to different calcitonins

Summary Calcitonin in the ultimobranchial gland of the dogfishScyliorhinus canicula cross-reacts with anti-dogfish, anti-salmon and anti-porcine calcitonin, but not with anti-human calcitonin, using indirect immunofluorescence procedures. These results do not reflect completely expectations derived from the primary structures of the hormones, where known, and from their physiological interrelationships.     

Retinal pigmentation, visual acuity and brightness levels.

This study investigates the hypothesis that the degree of retinal pigmentation in the human eye is adaptive as it relates to the maintenance of visual acuity in optically stressful environments, deserts and snowfields. Eighty-four subjects were examined, an estimation of their degree of retinal pigmentation made by ophthalmoscopic examination and their binocular visual acuity tested over ten levels of brightness. The general level of retinal pigmentation did not influence mean visual acuity within the levels of brightness used in this study. The hypothesis was, therefore, rejected, but with the proviso that this study should be extended to even higher levels of brightness than were obtained here. There was no difference in mean pupil size at various levels of illumination between individuals grouped by degree of retinal pigmentation.     

Ectopic expression of tyrosine hydroxylase in the pigmented epithelium rescues the retinal abnormalities and visual function common in albinos in the absence of melanin

Albino mammals have profound retinal abnormalities, including photoreceptor deficits and misrouted hemispheric pathways into the brain, demonstrating that melanin or its precursors are required for normal retinal development. Tyrosinase, the primary enzyme in melanin synthesis commonly mutated in albinism, oxidizes l-tyrosine to l-dopaquinone using l-3,4-dihydroxyphenylalanine (L-DOPA) as an intermediate product. L-DOPA is known to signal cell cycle exit during retinal development and plays an important role in the regulation of retinal development. Here, we have mimicked L-DOPA production by ectopically expressing tyrosine hydroxylase in mouse albino retinal pigment epithelium cells. Tyrosine hydroxylase can only oxidize l-tyrosine to L-DOPA without further progression towards melanin. The resulting transgenic animals remain phenotypically albino, but their visual abnormalities are corrected, with normal photoreceptor numbers and hemispheric pathways and improved visual function, assessed by an increase of spatial acuity. Our results demonstrate definitively that only early melanin precursors, L-DOPA or its metabolic derivatives, are vital in the appropriate development of mammalian retinae. They further highlight the value of substituting independent but biochemically related enzymes to overcome developmental abnormalities.     

A neural computation for visual acuity in the presence of eye movements

Humans can distinguish visual stimuli that differ by features the size of only a few photoreceptors. This is possible despite the incessant image motion due to fixational eye movements, which can be many times larger than the features to be distinguished. To perform well, the brain must identify the retinal firing patterns induced by the stimulus while discounting similar patterns caused by spontaneous retinal activity. This is a challenge since the trajectory of the eye movements, and consequently, the stimulus position, are unknown. We derive a decision rule for using retinal spike trains to discriminate between two stimuli, given that their retinal image moves with an unknown random walk trajectory. This algorithm dynamically estimates the probability of the stimulus at different retinal locations, and uses this to modulate the influence of retinal spikes acquired later. Applied to a simple orientation-discrimination task, the algorithm performance is consistent with human acuity, whereas naive strategies that neglect eye movements perform much worse. We then show how a simple, biologically plausible neural network could implement this algorithm using a local, activity-dependent gain and lateral interactions approximately matched to the statistics of eye movements. Finally, we discuss evidence that such a network could be operating in the primary visual cortex.     

Peripheral and central inputs shape network dynamics in the developing visual cortex in vivo

Spontaneous network activity constitutes a central theme during the development of neuronal circuitry [1, 2]. Before the onset of vision, retinal neurons generate waves of spontaneous activity that are relayed along the ascending visual pathway [3, 4] and shape activity patterns in these regions [5, 6]. The spatiotemporal nature of retinal waves is required to establish precise functional maps in higher visual areas, and their disruption results in enlarged axonal projection areas (e.g., [7-10]). However, how retinal inputs shape network dynamics in the visual cortex on the cellular level is unknown. Using in vivo two-photon calcium imaging, we identified two independently occurring patterns of network activity in the mouse primary visual cortex (V1) before and at the onset of vision. Acute manipulations of spontaneous retinal activity revealed that one type of network activity largely originated in the retina and was characterized by low synchronicity (L-) events. In addition, we identified a type of high synchronicity (H-) events that required gap junction signaling but were independent of retinal input. Moreover, the patterns differed in wave progression and developmental profile. Our data suggest that different activity patterns have complementary functions during the formation of synaptic circuits in the developing visual cortex.     

Effect of retinal ischemia on the non-image forming visual system

Retinal ischemic injury is an important cause of visual impairment. The loss of retinal ganglion cells (RGCs) is a key sign of retinal ischemic damage. A subset of RGCs expressing the photopigment melanopsin (mRGCs) regulates non-image-forming visual functions such as the pupillary light reflex (PLR), and circadian rhythms. We studied the effect of retinal ischemia on mRGCs and the non-image-forming visual system function. For this purpose, transient ischemia was induced by raising intraocular pressure to 120?mm Hg for 40?min followed by retinal reperfusion by restoring normal pressure. At 4 weeks post-treatment, animals were subjected to electroretinography and histological analysis. Ischemia induced a significant retinal dysfunction and histological alterations. At this time point, a significant decrease in the number of Brn3a(+) RGCs and in the anterograde transport from the retina to the superior colliculus and lateral geniculate nucleus was observed, whereas no differences in the number of mRGCs, melanopsin levels, and retinal projections to the suprachiasmatic nuclei and the olivary pretectal nucleus were detected. At low light intensity, a decrease in pupil constriction was observed in intact eyes contralateral to ischemic eyes, whereas at high light intensity, retinal ischemia did not affect the consensual PLR. Animals with ischemia in both eyes showed a conserved locomotor activity rhythm and a photoentrainment rate which did not differ from control animals. These results suggest that the non-image forming visual system was protected against retinal ischemic damage.     

The Visual Cycle in the Inner Retina of Chicken and the Involvement of Retinal G-Protein-Coupled Receptor (RGR)

The vertebrate retina contains typical photoreceptor (PR) cones and rods responsible for day/night vision, respectively, and intrinsically photosensitive retinal ganglion cells (ipRGCs) involved in the regulation of non-image-forming tasks. Rhodopsin/cone opsin photopigments in visual PRs or melanopsin (Opn4) in ipRGCs utilizes retinaldehyde as a chromophore. The retinoid regeneration process denominated as “visual cycle” involves the retinal pigment epithelium (RPE) or Müller glial cells. Opn4, on the contrary, has been characterized as a bi/tristable photopigment, in which a photon of one wavelength isomerizes 11-cis to all-trans retinal (Ral), with a second photon re-isomerizing it back. However, it is unknown how the chromophore is further metabolized in the inner retina. Nor is it yet clear whether an alternative secondary cycle occurs involving players such as the retinal G-protein-coupled receptor (RGR), a putative photoisomerase of unidentified inner retinal activity. Here, we investigated the role of RGR in retinoid photoisomerization in Opn4x (Xenopus ortholog) (+) RGC primary cultures free of RPE and other cells from chicken embryonic retinas. Opn4x (+) RGCs display significant photic responses by calcium fluorescent imaging and photoisomerize exogenous all-trans to 11-cis Ral and other retinoids. RGR was found to be expressed in developing retina and in primary cultures; when its expression was knocked down, the levels of 11-cis, all-trans Ral, and all-trans retinol in cultures exposed to light were significantly higher and those in all-trans retinyl esters lower than in dark controls. The results support a novel role for RGR in ipRGCs to modulate retinaldehyde levels in light, keeping the balance of inner retinal retinoid pools.     

The role of primary cilia in the development and disease of the retina

The normal development and function of photoreceptors is essential for eye health and visual acuity in vertebrates. Mutations in genes encoding proteins involved in photoreceptor development and function are associated with a suite of inherited retinal dystrophies, often as part of complex multi-organ syndromic conditions. In this review, we focus on the role of the photoreceptor outer segment, a highly modified and specialized primary cilium, in retinal health and disease. We discuss the many defects in the structure and function of the photoreceptor primary cilium that can cause a class of inherited conditions known as ciliopathies, often characterized by retinal dystrophy and degeneration, and highlight the recent insights into disease mechanisms.     

The role of primary cilia in the development and disease of the retina

The normal development and function of photoreceptors is essential for eye health and visual acuity in vertebrates. Mutations in genes encoding proteins involved in photoreceptor development and function are associated with a suite of inherited retinal dystrophies, often as part of complex multi-organ syndromic conditions. In this review, we focus on the role of the photoreceptor outer segment, a highly modified and specialized primary cilium, in retinal health and disease. We discuss the many defects in the structure and function of the photoreceptor primary cilium that can cause a class of inherited conditions known as ciliopathies, often characterized by retinal dystrophy and degeneration, and highlight the recent insights into disease mechanisms.     

The photoreceptor system in the retinae of two dogfishes, Scyliorhinus canicula and Galeus melastomus: possible relationship with depth distribution and predatory lifestyle

The small spotted dogfish Scyliorhinus canicula and the blackmouth dogfish Galeus melastomus, whose depth distributions overlap in the upper part of the slope (c. 500 m depth), where they have access to the same prey community, have well‐developed eyes and a pure‐rod retina with a single layer of photoreceptors. Interspecific differences in rod outer segment length (L_ROS) within retinal regions were found. In the periphery and the retinal centre G. melastomus showed a L_ROS 24 and 30% longer, respectively, than S. canicula and, therefore, a potential for increased sensitivity. In both species longer L_ROS were always found in correspondence with the retinal centre where the ganglion cell topography formed a horizontal meridian that allowed for better discrimination of the horizon in the visual field. In this area L_ROS reached 53·4±4·1μm in S. canicula and 77·1±10·5μm in G. melastomus against 46·3±4·2μm and 61·1±10·1μm in the retinal periphery. No significant differences were recorded in L_ROS and rod density during growth. In both species, a rapid increase of theoretical visual acuity was found to be related to an increase in fish L_T and lens size. Visual acuity ranged between 1·7 and 3 cycles degree^‐1 in S. canicula and 2·4 and 4·2 in G. melastomus. The G. melastomus rod visual pigment showed the characteristic spectral adaptation to vision in deep‐water (λ_max of 481 nm), but was also well placed to detect the bioluminescence of some of its main prey species. In S. canicula the visual pigment absorption (λ_max of 496 nm) was more typical of shallow water living fishes. The opsin sequences of the two visual pigments are discussed and key amino acid sites were identified where sequence changes could be responsible for the spectral absorption differences between the two species. The possible relationship between L^ROS, visual acuity, visual pigment absorption, depth distribution and feeding behaviour are discussed.     

Spontaneous retinal activity mediates development of ocular dominance columns and binocular receptive fields in v1

The mechanisms that give rise to ocular dominance columns (ODCs) during development are controversial. Early experiments indicated a key role for retinal activity in ODC formation. However, later studies showed that in those early experiments, the retinal activity perturbation was initiated after ODCs had already formed. Moreover, recent studies concluded that early eye removals do not impact ODC segregation. Here we blocked spontaneous retinal activity during the very early stages of ODC development. This permanently disrupted the anatomical organization of ODCs and led to a dramatic increase in receptive field size for binocular cells in primary visual cortex. Our data suggest that early spontaneous retinal activity conveys crucial information about whether thalamocortical axons represent one or the other eye and that this activity mediates binocular competition important for shaping receptive fields in primary visual cortex.     

Photoisomerization mechanism of rhodopsin and 9-cis-rhodopsin revealed by x-ray crystallography

The primary photochemical process of the visual function has been investigated using the three crystallographic models, 11-cis-rhodopsin, all-trans-bathorhodopsin, and the artificial isomeric 9-cis-rhodopsin. Detailed examination of the atomic displacements and dihedral angle changes of the retinal chromophore involved in the interconversion among these isomers suggests the mechanism of isomerization efficiency.     

The relationship of retrobulbar hematomas to vision in cynomolgus monkeys

An experimental model has been developed to measure the effect of retrobulbar hematomas on functional vision in cynomolgus monkeys. In this model, functional vision was quantitated using flashed evoked visual potentials in five monkeys following creation of retrobulbar hematomas. In one monkey used as a control, functional vision remained impaired for 180 minutes following induction of retinal ischemia by increased intraorbital pressure. In two monkeys in which increased intraorbital pressure was relieved by anterior chamber paracentesis following 15 minutes of retinal ischemia, flashed evoked visual potential promptly returned to baseline level. In two additional monkeys in which increased intraorbital pressure was relieved following 30 minutes of retinal ischemia, flashed evoked visual potentials improved but never returned to baseline levels. This study demonstrates the usefulness of flashed evoked visual potentials in measuring functional vision in cynomolgus monkeys. This experimental model should prove useful in evaluating the effects of increased intraorbital pressure on functional vision and the effect of intervention on impaired vision due to retrobulbar hematomas. Further studies with larger numbers of animals are needed to clarify these preliminary studies and document longer-term effects of retinal ischemia secondary to retrobulbar hematomas.     

Serine 85 in transmembrane helix 2 of short-wavelength visual pigments interacts with the retinylidene Schiff base counterion.

Short-wavelength cone visual pigments (SWS1) are responsible for detecting light from 350 to 430 nm. Models of this class of pigment suggest that TM2 has extensive contacts with the retinal binding pocket and stabilizes interhelical interactions. The role of TM2 in the structure-function of the Xenopus SWS1 (VCOP, lambda(max) = 427 nm) pigment was studied by replacement of the helix with that of bovine rhodopsin and also by mutagenesis of highly conserved residues. The TM2 chimera and G78D, F79L, M81E, P88T, V89S, and F90V mutants did not produce any significant spectral shift of the dark state or their primary photointermediate formed upon illumination at cryogenic temperatures. The mutant G77R (responsible for human tritanopia) was completely defective in folding, while C82A and F87T bound retinal at reduced levels. The position S85 was crucial for obtaining the appropriate spectroscopic properties of VCOP. S85A and S85T did not bind retinal. S85D bound retinal and had a wild-type dark state at room temperature and a red-shifted dark state at 45 K and formed an altered primary photointermediate. S85C absorbed maximally at 390 nm at neutral pH and at 365 nm at pH >7.5. The S85C dark state was red shifted by 20 nm at 45 K and formed an altered primary photointermediate. These data suggest that S85 is involved in a hydrogen bond with the protonated retinylidene Schiff base counterion in both the dark state and the primary photointermediate.     

Illuminating synapses and circuitry in the retina

In the central nervous system, space is at a premium. This is especially true in the retina, where synapses, cells, and circuitry have evolved to maximize signal-processing capacity within a thin, optically transparent tissue. For example, at some retinal synapses, single presynaptic active zones contact multiple postsynaptic targets; some individual neurons perform completely different tasks depending on visual conditions, while others execute hundreds of circuit computations in parallel; and the retinal network adapts, at various levels, to the ever-changing visual world. Each of these features reflects efficient use of limited cellular resources to optimally encode visual information.     

A direct projection from area V1 to area V3A of rhesus monkey visual cortex

Small cortical lesions were made in regions of the primary visual cortex (V1) representing different retinal eccentricities. It was found that, whereas all parts of V1 project to visual areas V2, V3 and the motion area of the superior temporal sulcus, only parts of V1 representing peripheral eccentricities (in excess of 30 degrees) project directly to visual area V3A.     

Primary optic projections in the rabbit. Study using the horseradish peroxidase anterograde labeling technic

The primary visual pathways, in particular those to the lateral geniculate body, of 11 albino and 7 pigmented rabbits, were studied using the method of anterograde labelling with horseradish peroxidase following injection of the tracer into the vitreous body of one eye. A heavy projection to the contralateral dorsal lateral geniculate nucleus was seen in all animals. In both albino and pigmented animals a region devoid of label was present in the medial part of the alpha sector of the nucleus. This region corresponded to a compact, oval or wedge-shaped field of terminal label in the ipsilateral nucleus, which was much heavier in pigmented than in albino rabbits. In the ventral lateral geniculate nucleus, contralateral retinal input was almost entirely confined to the caudal half of the lateral sector of the nucleus, where two laminae of dense terminal label, separated by a less densely labelled area, were oriented parallel to one another and to the optic tract. This bilaminar distribution of retinal afferents to the ventral lateral geniculate nucleus has not been described in previous studies. The ipsilateral projection was to the dorsal part of the lateral sector and was most prominent in pigmented animals. The "intergeniculate leaflet" received a prominent contralateral input in all animals, and a clear ipsilateral input in pigmented animals, which overlapped with the contralateral input. Projections to other primary visual centres (pretectal nuclei, superior colliculus, nuclei of the accessory optic tract) are also described.