Ventral Retina Research Articles

The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells

The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. Because Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2-/- mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity.

Ipsilateral and Contralateral Retinal Ganglion Cells Express Distinct Genes during Decussation at the Optic Chiasm.

The increasing availability of transcriptomic technologies within the last decade has facilitated high-throughput identification of gene expression differences that define distinct cell types as well as the molecular pathways that drive their specification. The retinal projection neurons, retinal ganglion cells (RGCs), can be categorized into distinct morphological and functional subtypes and by the laterality of their projections. Here, we present a method for purifying the sparse population of ipsilaterally projecting RGCs in mouse retina from their contralaterally projecting counterparts during embryonic development through rapid retrograde labeling followed by fluorescence-activated cell sorting. Through microarray analysis, we uncovered the distinct molecular signatures that define and distinguish ipsilateral and contralateral RGCs during the critical period of axonal outgrowth and decussation, with more than 300 genes differentially expressed within these two cell populations. Among the differentially expressed genes confirmed through in vivo expression validation, several genes that mark "immaturity" are expressed within postmitotic ipsilateral RGCs. Moreover, at least one complementary pair, Igf1 and Igfbp5, is upregulated in contralateral or ipsilateral RGCs, respectively, and may represent signaling pathways that determine ipsilateral versus contralateral RGC identity. Importantly, the cell cycle regulator cyclin D2 is highly expressed in peripheral ventral retina with a dynamic expression pattern that peaks during the period of ipsilateral RGC production. Thus, the molecular signatures of ipsilateral and contralateral RGCs and the mechanisms that regulate their differentiation are more diverse than previously expected.

Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina.

We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5–10 μg NMDA caused 30–50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina.

Two UV-Sensitive Photoreceptor Proteins, Opn5m and Opn5m2 in Ray-Finned Fish with Distinct Molecular Properties and Broad Distribution in the Retina and Brain.

Opn5 is a group within the opsin family of proteins that is responsible for visual and non-visual photoreception in animals. It consists of several subgroups, including Opn5m, the only subgroup containing members found in most vertebrates, including mammals. In addition, recent genomic information has revealed that some ray-finned fishes carry paralogous genes of Opn5m while other fishes have no such genes. Here, we report the molecular properties of the opsin now called Opn5m2 and its distributions in both the retina and brain. Like Opn5m, Opn5m2 exhibits UV light-sensitivity when binding to 11-cis-retinal and forms a stable active state that couples with Gi subtype of G protein. However, Opn5m2 does not bind all-trans-retinal and exhibits exclusive binding to 11-cis-retinal, whereas many bistable opsins, including fish Opn5m, can bind directly to all-trans-retinal as well as 11-cis-retinal. Because medaka fish has lost the Opn5m2 gene from its genome, we compared the tissue distribution patterns of Opn5m in medaka fish, zebrafish, and spotted gar, in addition to the distribution patterns of Opn5m2 in zebrafish and spotted gar. Opn5m expression levels showed a gradient along the dorsal–ventral axis of the retina, and preferential expression was observed in the ventral retina in the three fishes. The levels of Opn5m2 showed a similar gradient with preferential expression observed in the dorsal retina. Opn5m expression was relatively abundant in the inner region of the inner nuclear layer, while Opn5m2 was expressed in the outer edge of the inner nuclear layer. Additionally, we could detect Opn5m expression in several brain regions, including the hypothalamus, of these fish species. Opn5m2 expression could not be detected in zebrafish brain, but was clearly observed in limited brain regions of spotted gar. These results suggest that ray-finned fishes can generally utilize UV light information for non-image-forming photoreception in a wide range of cells in the retina and brain.

Compound eye and ocellar structure for walking and flying modes of locomotion in the Australian ant, Camponotus consobrinus.

Ants are unusual among insects in that individuals of the same species within a single colony have different modes of locomotion and tasks. We know from walking ants that vision plays a significant role in guiding this behaviour, but we know surprisingly little about the potential contribution of visual sensory structures for a flying mode of locomotion. Here we investigate the structure of the compound eye and ocelli in pedestrian workers, alate females and alate males of an Australian ant, Camponotus consobrinus, and discuss the trade-offs involved in optical sensitivity and spatial resolution. Male ants have more but smaller ommatidia and the smallest interommatidial angles, which is most likely an adaptation to visually track individual flying females. Both walking and flying forms of ants have a similar proportion of specialized receptors sensitive to polarized skylight, but the absolute number of these receptors varies, being greatest in males. Ocelli are present only in the flying forms. Each ocellus consists of a bipartite retina with a horizon-facing dorsal retina, which contains retinula cells with long rhabdoms, and a sky-facing ventral retina with shorter rhabdoms. We discuss the implications of these and their potential for sensing the pattern of polarized skylight.

Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish.

The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. Here we elucidate the role of RA in differential regulation of the tandemly-duplicated long wavelength-sensitive (LWS) cone opsin genes. Zebrafish embryos were treated with RA from 48 hours post-fertilization (hpf) to 75 hpf, and RNA was isolated from eyes for microarray analysis. ~170 genes showed significantly altered expression, including several transcription factors and components of cellular signaling pathways. Of interest, the LWS1 opsin gene was strongly upregulated by RA. LWS1 is the upstream member of the tandemly duplicated LWS opsin array and is normally not expressed embryonically. Embryos treated with RA 48 hpf to 100 hpf or beyond showed significant reductions in LWS2-expressing cones in favor of LWS1-expressing cones. The LWS reporter line, LWS-PAC(H) provided evidence that individual LWS cones switched from LWS2 to LWS1 expression in response to RA. The RA signaling reporter line, RARE:YFP indicated that increased RA signaling in cones was associated with this opsin switch, and experimental reduction of RA signaling in larvae at the normal time of onset of LWS1 expression significantly inhibited LWS1 expression. A role for endogenous RA signaling in regulating differential expression of the LWS genes in postmitotic cones was further supported by the presence of an RA signaling domain in ventral retina of juvenile zebrafish that coincided with a ventral zone of LWS1 expression. This is the first evidence that an extracellular signal may regulate differential expression of opsin genes in a tandemly duplicated array.

Variations in retinal photoreceptor topography and the organization of the rod-free zone reflect behavioral diversity in Australian passerines.

The avian retina possesses one of the most diverse complements of photoreceptor types among vertebrates but little is known about their spatial distribution. Here we used retinal wholemounts and stereological methods to present the first complete maps of the topographic distribution of rods and cones in four species of Australian passerines with diverse trophic specializations. All species studied have one central and one temporal rod-free zone. In the insectivorous yellow-rumped thornbill, the central rod-free zone is unusually large, occupying ∼17% (56°) of the retinal area (angular subtense), whereas in nectarivorous and frugivorous species it represents only ∼0.1% (5-7°) to 0.3% (10°) of the retinal area (angular subtense). In contrast, the temporal rod-free zone varies little between species (∼0.02-0.4%; 2-10°). In all species, rods follow a pronounced dorsoventral gradient with highest densities in the ventral retina. The topographic distribution of cones is concentric and reveals a central fovea and a temporal area. In the yellow-rumped thornbill, cone densities form an extended plateau surrounding the fovea, beyond which densities fall rapidly towards the retinal periphery. For the other species, cone densities decline gradually along a foveal to peripheral gradient. Estimates of spatial resolving power calculated using cone peak densities are higher in the central fovea (19-41 cycles/degree) than in the temporal area (9-15 cycles/degree). In conclusion, we suggest that the unusual organization of the rod-free zone and the distinct topographic distribution of rods and cones correlate with specific ecological needs for enhanced visual sensitivity and spatial resolution in these birds.

Differential responsiveness of distinct retinal domains to Atoh7

During vertebrate eye development retinal progenitor cells (RPCs) differentiate into all neural cell types of the retina. Retinal ganglion cells (RGCs) represent the first cell type to be generated. For their development, Atoh7, a basic Helix Loop Helix (bHLH) transcription factor is crucial. Atoh7 loss of function results in a massive reduction or even a total loss of RGCs. However, inconsistent results have been obtained in atoh7 gain of function experiments with respect to ganglion cell genesis, implying that the effect of Atoh7 is likely to be dependent on the competence state of the RPC.In this study we addressed the differential susceptibilities of early RPCs to Atoh7 in vivo, using medaka. Unexpectedly, we observed a largely normal development of the dorsal retina, although atoh7 was precociously expressed. However, the development of the retina close to the optic nerve head (part of the ventral retina) was disturbed severely. Photoreceptors were largely absent and the Müller glia cell number was reduced significantly. The majority of cells in this domain were ganglion cells and the abnormal development of this area affected the closure of the optic fissure resulting in coloboma.

Differences in Neural Circuitry Guiding Behavioral Responses to Polarized light Presented to Either the Dorsal or Ventral Retina in Drosophila

Linearly polarized light (POL) serves as an important cue for many animals, providing navigational information, as well as directing them toward food sources and reproduction sites. Many insects detect the celestial polarization pattern, or the linearly polarized reflections off of surfaces, such as water. Much progress has been made toward characterizing both retinal detectors and downstream circuit elements responsible for celestial POL vision in different insect species, yet much less is known about the neural basis of how polarized reflections are detected. We previously established a novel, fully automated behavioral assay for studying the spontaneous orientation response of Drosophila melanogaster populations to POL stimuli presented to either the dorsal, or the ventral halves of the retina. We identified separate retinal detectors mediating these responses: the ‘Dorsal Rim Area’ (DRA), which had long been implicated in celestial POL vision, as well as a previously uncharacterized ‘ventral polarization area’ (VPA). In this study, we investigate whether DRA and VPA use the same or different downstream circuitry, for mediating spontaneous behavioral responses. We use homozygous mutants, or molecular genetic circuit-breaking tools (silencing, as well as rescue of synaptic activity), in combination with our behavioral paradigm. We show that responses to dorsal versus ventral stimulation involve previously characterized optic lobe neurons, like lamina monopolar cell L2 and medulla cell types Dm8/Tm5c. However, using different experimental conditions, we show that important differences exist between the requirement of these cell types downstream of DRA versus VPA. Therefore, while the neural circuits underlying behavioral responses to celestial and reflected POL cues share important building blocks, these elements play different functional roles within the network.

Death by color: differential cone loss in the aging mouse retina

Differential cell death is a common feature of aging and age-related disease. In the retina, 30% of rod photoreceptors are lost over life in humans and rodents. However, studies have failed to show age-related cell death in mouse cone photoreceptors, which is surprising because cone physiological function declines with age. Moreover in human, differential loss of short wavelength cone function is an aspect of age-related retinal disease. Here, cones are examined in young (3-month-old) and aged (12-month-old) C57 mice and also in complement factor H knock out mice (CFH−/−) that have been proposed as a murine model of age-related macular degeneration. In vivo imaging showed significant age-related reductions in outer retinal thickness in both groups over this period. Immunostaining for opsins revealed a specific significant decline of >20% for the medium/long (M/L)-wavelength cones but only in the periphery. S cones numbers were not significantly affected by age. This differential cell loss was backed up with quantitative real-time polymerase chain reaction for the 2 opsins, again showing S opsin was unaffected, but that M/L opsin was reduced particularly in CFH−/− mice. These results demonstrate aged cone loss, but surprisingly, in both genotypes, it is only significant in the peripheral ventral retina and focused on the M/L population and not S cones. We speculate that there may be fundamental differences in differential cone loss between human and mouse that may question the validity of mouse models of human outer retinal aging and pathology.

The visual ecology of a deep-sea fish, the escolar Lepidocybium flavobrunneum (Smith, 1843)

Escolar (Lepidocybium flavobrunneum, family Gempylidae) are large and darkly coloured deep-sea predatory fish found in the cold depths (more than 200 m) during the day and in warm surface waters at night. They have large eyes and an overall low density of retinal ganglion cells that endow them with a very high optical sensitivity. Escolar have banked retinae comprising six to eight layers of rods to increase the optical path length for maximal absorption of the incoming light. Their retinae possess two main areae of higher ganglion cell density, one in the ventral retina viewing the dorsal world above (with a moderate acuity of 4.6 cycles deg(-1)), and the second in the temporal retina viewing the frontal world ahead. Electrophysiological recordings of the flicker fusion frequency (FFF) in isolated retinas indicate that escolar have slow vision, with maximal FFF at the highest light levels and temperatures (around 9 Hz at 23°C) which fall to 1-2 Hz in dim light or cooler temperatures. Our results suggest that escolar are slowly moving sit-and-wait predators. In dim, warm surface waters at night, their slow vision, moderate dorsal resolution and highly sensitive eyes may allow them to surprise prey from below that are silhouetted in the downwelling light.

Ocellar structure and neural innervation in the honeybee

Honeybees have a visual system composed of three ocelli (simple eyes) located on the top of the head, in addition to two large compound eyes. Although experiments have been conducted to investigate the role of the ocelli within the visual system, their optical characteristics, and function remain controversial. In this study, we created three-dimensional (3-D) reconstructions of the honeybee ocelli, conducted optical measurements and filled ocellar descending neurons to assist in determining the role of ocelli in honeybees. In both the median and lateral ocelli, the ocellar retinas can be divided into dorsal and ventral parts. Using the 3-D model we were able to assess the viewing angles of the retinas. The dorsal retinas view the horizon while the ventral retinas view the sky, suggesting quite different roles in attitude control. We used the hanging drop technique to assess the spatial resolution of the retinas. The lateral ocelli have significantly higher spatial resolution compared to the median ocellus. In addition, we established which ocellar retinas provide the input to five pairs of large ocellar descending neurons. We found that four of the neuron pairs have their dendritic fields in the dorsal retinas of the lateral ocelli, while the fifth has fine dendrites in the ventral retina. One of the neuron pairs also sends very fine dendrites into the border region between the dorsal and ventral retinas of the median ocellus.

Adaptation to Background Light Enables Contrast Coding at Rod Bipolar Cell Synapses

Rod photoreceptors contribute to vision over an ∼ 6-log-unit range of light intensities. The wide dynamic range of rod vision is thought to depend upon light intensity-dependent switching between two parallel pathways linking rods to ganglion cells: a rod → rod bipolar (RB) cell pathway that operates at dim backgrounds and a rod → cone → cone bipolar cell pathway that operates at brighter backgrounds. We evaluated this conventional model of rod vision by recording rod-mediated light responses from ganglion and AII amacrine cells and by recording RB-mediated synaptic currents from AII amacrine cells in mouse retina. Contrary to the conventional model, we found that the RB pathway functioned at backgrounds sufficient to activate the rod → cone pathway. As background light intensity increased, the RB's role changed from encoding the absorption of single photons to encoding contrast modulations around mean luminance. This transition is explained by the intrinsic dynamics of transmission from RB synapses.

Ten-m2 Is Required for the Generation of Binocular Visual Circuits

Functional binocular vision requires that inputs arising from the two retinae are integrated and precisely organized within central visual areas. Previous studies have demonstrated an important role for one member of the Ten-m/Odz/teneurin family, Ten-m3, in the mapping of ipsilateral retinal projections. Here, we have identified a distinct role for another closely related family member, Ten-m2, in the formation of the ipsilateral projection in the mouse visual system. Ten-m2 expression was observed in the retina, dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and primary visual cortex (V1) of the developing mouse. Anterograde and retrograde tracing experiments in Ten-m2 knock-out (KO) mice revealed a specific decrease in ipsilateral retinal ganglion cells projecting to dLGN and SC. This reduction was most prominent in regions corresponding to ventral retina. No change in the topography of ipsilateral or contralateral projections was observed. While expression of a critical ipsilateral fate determinant, Zic2, appeared unaltered, a notable reduction in one of its downstream targets, EphB1, was observed in ventral retina, suggesting that Ten-m2 may interact with this molecular pathway. Immunohistochemistry for c-fos, a neural activity marker, revealed that the area of V1 driven by ipsilateral inputs was reduced in KOs, while the ratio of ipsilateral-to-contralateral responses contributing to binocular activation during visually evoked potential recordings was also diminished. Finally, a novel two-alternative swim task revealed specific deficits associated with dorsal visual field. These data demonstrate a requirement for Ten-m2 in the establishment of ipsilateral projections, and thus the generation of binocular circuits, critical for mammalian visual function.

Retinal Region of Polarization Sensitivity Switches during Ontogeny of Rainbow Trout

Polarization sensitivity (PS) in vertebrate vision is controversial, perhaps because its underlying mechanism has remained obscure. An issue that might have added to the controversy is that rainbow trout (Oncorhynchus mykiss), which have served as the primary model system for polarization-based orientation, lose their ability to orient relative to celestial polarized-light patterns when parr (fry) transform into migratory smolts (juveniles), which would benefit most from polarization-based orientation. Here we addressed two key questions: (1) what is the mechanism underling PS?, and (2) how can the paradoxical loss of PS in trout smolts be reconciled? We assessed PS from optic nerve recordings in parr and smolts and found that the retinal region with enhanced PS shifted from the ventral retina in parr to the dorsal retina in smolts. This adaptation may allow fish to use the most reliable polarization field encountered at each life stage, the celestial polarization field in the shallow-swimming parr and the depth-insensitive underwater polarization field in the deep-swimming smolts. In addition, we assessed spectral sensitivity across the retina and during ontogeny and fit a cascade retinal model to PS data. We found that differential contribution of two cone detectors with orthogonal PS could drive the variation in PS and that feedback from horizontal cells to cones could explain the differential amplification of PS. This elegant arrangement, in which weak PS of cones is amplified and tuned by retinal networks, allows for PS without interfering with sampling of other visual information and illustrates how sensory systems may simultaneously process disparate aspects of physical environments.

Chromatic Coding from Cone-type Unselective Circuits in the Mouse Retina

Retinal specializations such as cone-photoreceptor opsin-expression gradients, as found in several vertebrate species, are intuitively considered detrimental to color vision. In mice, the majority of cones coexpress both "blue" and "green" opsin. The coexpression ratio changes along the dorsoventral axis, resulting in a "green"-dominant dorsal and a "blue"-dominant ventral retina. Here, we asked how these specializations affect chromatic processing, especially with respect to the opsin transitional zone, the band where opsin coexpression shifts from "green" to "blue." Using electrophysiology, modeling, and calcium imaging, we found that "alpha-like" retinal ganglion cells, which previously have not been implicated in chromatic processing, display color-opponent responses when located in the vicinity of the opsin transitional zone. Moreover, direction-selective ganglion cells within this zone respond differentially to color sequences. Our data suggest that the dorsoventral opsin distribution, in combination with conventional spatiotemporal processing, renders mouse ganglion cell responses color-opponent without requiring cone-type selective connectivity.

Form and Function of the M4 Cell, an Intrinsically Photosensitive Retinal Ganglion Cell Type Contributing to Geniculocortical Vision

The photopigment melanopsin confers photosensitivity upon a minority of retinal output neurons. These intrinsically photosensitive retinal ganglion cells (ipRGCs) are more diverse than once believed, comprising five morphologically distinct types, M1 through M5. Here, in mouse retina, we provide the first in-depth characterization of M4 cells, including their structure, function, and central projections. M4 cells apparently correspond to ON α cells of earlier reports, and are easily distinguished from other ipRGCs by their very large somata. Their dendritic arbors are more radiate and highly branched than those of M1, M2, or M3 cells. The melanopsin-based intrinsic photocurrents of M4 cells are smaller than those of M1 and M2 cells, presumably because melanopsin is more weakly expressed; we can detect it immunohistochemically only with strong amplification. Like M2 cells, M4 cells exhibit robust, sustained, synaptically driven ON responses and dendritic stratification in the ON sublamina of the inner plexiform layer. However, their stratification patterns are subtly different, with M4 dendrites positioned just distal to those of M2 cells and just proximal to the ON cholinergic band. M4 receptive fields are large, with an ON center, antagonistic OFF surround and nonlinear spatial summation. Their synaptically driven photoresponses lack direction selectivity and show higher ultraviolet sensitivity in the ventral retina than in the dorsal retina, echoing the topographic gradient in S- and M-cone opsin expression. M4 cells are readily labeled by retrograde transport from the dorsal lateral geniculate nucleus and thus likely contribute to the pattern vision that persists in mice lacking functional rods and cones.

Chemical Chaperone TUDCA Preserves Cone Photoreceptors in a Mouse Model of Leber Congenital Amaurosis

Mutations in either retinoid isomerase (RPE65) or lecithin-retinol acyltransferase (LRAT) lead to Leber congenital amaurosis (LCA). By using the Lrat(-/-) mouse model, previous studies have shown that the rapid cone degeneration in LCA was caused by endoplasmic reticulum (ER) stress induced by S-opsin aggregation. The purpose of this study is to examine the efficacy of an ER chemical chaperone, tauroursodeoxycholic acid (TUDCA), in preserving cones in the Lrat(-/-) model. Lrat(-/-) mice were systemically administered with TUDCA and vehicle (0.15 M NaHCO(3)) every 3 days from P9 to P28. Cone cell survival was determined by counting cone cells on flat-mounted retinas. The expression and subcellular localization of cone-specific proteins were analyzed by western blotting and immunohistochemistry, respectively. TUDCA treatment reduced ER stress and apoptosis in Lrat(-/-) retina. It significantly slowed down cone degeneration in Lrat(-/-) mice, resulting in a ∼3-fold increase in cone density in the ventral and central retina as compared with the vehicle-treated mice at P28. Furthermore, TUDCA promoted the degradation of cone membrane-associated proteins by enhancing the ER-associated protein degradation pathway. Systemic injection of TUDCA is effective in reducing ER stress, preventing apoptosis, and preserving cones in Lrat(-/-) mice. TUDCA has the potential to lead to the development of a new class of therapeutic drugs for treating LCA.

Retinal neural progenitors express topographic map markers

Transplantation of neural stem cells for replacing neurons after neurodegeneration requires that the transplanted stem cells accurately reestablish the lost neural circuits in order to restore function. Retinal ganglion cell axons project to visual centers of the brain forming circuits in precise topographic order. In chick, dorsal retinal neurons project to ventral optic tectum, ventral neurons to dorsal tectum, anterior neurons to posterior tectum and posterior neurons to anterior tectum; forming a continuous point-to-point map of retinal cell position in the tectal projection. We found that when stem cells derived from ventral retina were implanted in dorsal host retina, the stem cells that became ganglion cells projected to dorsal tectum, appropriate for their site of origin in retina but not appropriate for their site of implant in retina. This led us to ask if retinal progenitors exhibit topographic markers of cell position in retina. Indeed, retinal neural progenitors express topographic markers: dorsal stem cells expressed more Ephrin B2 than ventral stem cells and, conversely, ventral stem cells expressed more Pax-2 and Ventroptin than dorsal stem cells. The fact that neural progenitors express topographic markers has pertinent implications in using neural stem cells in cell replacement therapy for replacing projecting neurons that express topographic order, e.g., analogous neurons of the visual, auditory, somatosensory and motor systems.

Photoreceptor types, visual pigments, and topographic specializations in the retinas of hydrophiid sea snakes

Sea snakes have evolved numerous anatomical, physiological, and behavioral adaptations to suit their wholly aquatic lifestyle. However, although sea snakes use vision for foraging and mate selection, little is known about their visual abilities. We used microspectrophotometry, light microscopy, and scanning electron microscopy to characterize the retinal photoreceptors of spine-bellied (Lapemis curtus) and horned (Acalyptophis peronii) sea snakes. Both species have three types of visual pigment sensitive to short (SWS; wavelength of maximum absorbance, λmax 428-430 nm), medium (MWS; λmax 496 nm), and long wavelengths of light (LWS; λmax 555-559 nm) in each of three different subtypes of cone-like single photoreceptor. They also possess a cone-like double photoreceptor subtype, both the principal and accessory member of which contain the LWS visual pigment. Conventional rods were not observed, although the MWS photoreceptor may be a "transmuted" rod. We also used stereology to measure the total number and topographic distribution of neurons in the ganglion cell layer of L. curtus, the olive sea snake (Aipysurus laevis), and the olive-headed sea snake (Disteira major). All species have a horizontal visual streak with specialized areas in the nasal and temporal retina. Both L. curtus and D. major also have a specialized area in the ventral retina, which may reflect differences in habitat usage and/or foraging behavior compared to A. laevis. Maximal spatial resolution was estimated at 1.1, 1.6, and 2.3 cycles deg⁻¹ in D. major, L. curtus, and A. laevis, respectively; the superior value for A. laevis may reflect its specialized crevice-foraging hunting technique.