Light sensitivity in a vertebrate mechanoreceptor?

Using immunohistochemistry and western blot analysis, we demonstrate that melanopsin is localised in cells around the central pore of lateral line neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a known photoreceptor pigment with diverse functions in vertebrates, we suggest that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor, might also be light sensitive. Potential functions of such photosensitivity are discussed, including its role in mediating locomotor responses following dermal illumination.

The eyes of the deep diving hooded seal (Cystophora cristata) enhance sensitivity to ultraviolet light.

The mammalian visual range is approximately 400-700 nm, although recent evidence suggests varying ultraviolet (UV) extensions in diverse terrestrial species. UV sensitivity may have advantages in the dim, blue light shifted environment experienced by submerged marine mammals. It may also be advantageous when seals are on land as UV is reflected by snow and ice but absorbed by fur, enhancing visual contrast. Here we show that the pelagic hooded seal (Cystophora cristata) has a highly UV permissive cornea and lens. Seals like other carnivores have a tapetum lucidum (TL) reflecting light back through the retina increasing sensitivity. The TL in this seal is unusual being white and covering almost the entire retina unlike that in other carnivores. Spectral reflectance from its surface selectively increases the relative UV/blue components >10 times than other wavelengths. Retinal architecture is consistent with a high degree of convergence. Enhanced UV from a large TL surface with a high degree of retinal convergence will increase sensitivity at a cost to acuity. UV electrophysiological retina responses were only obtained to dim, rod mediated stimuli, with no evidence of cone input. As physiological measurements of threshold sensitivity are much higher than those for psychophysical detection, these seals are likely to be more UV sensitive than our results imply. Hence, UV reflections from the TL will afford increased sensitivity in dim oceanic environments.

Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.

Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF) visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP) mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies.

A latitudinal cline in the efficacy of endogenous signals: evidence derived from retinal cone contraction in fish.

Like many physiological systems synchronised to the light:dark cycle, retinomotor movements in 'lower' vertebrates are controlled by both the ambient illumination and input from endogenous circadian oscillators. In the present study, we examine the relative influence of these two signals in various species of teleost fish with different latitudes of origin. We find equatorial species show very strong endogenous control. The cones of the glowlight tetra, for example, continue to go through undiminished cycles of contraction and relaxation that mirror the previous light:dark cycle for at least two weeks in continual darkness. To quantify the relative effectiveness of the ambient light compared with endogenous signals in causing cone contraction, the degree to which seven teleost species responded to light during the dark phase of their light:dark cycle was examined. In this situation the retina receives conflicting instructions; while the light is acting directly to cause light adaptation, any endogenous signal tends to keep the retinal elements dark adapted. The further from the equator a species originated, the more its cones contracted in response to such illumination, suggesting animals from higher latitudes make little use of endogenous oscillators and rely more on ambient illumination to control behaviours. Equatorial species, however, rely on internal pacemakers to a much greater degree and are relatively insensitive to exogenous light signals. Because these data are consistent with published observations in systems as diverse as melatonin synthesis in Arctic reindeer and the behaviour of regional populations of Drosophila, latitudinal clines in the efficacy of circadian oscillators may be a common feature among animals.

Genetic ablation of retinal pigment epithelial cells reveals the adaptive response of the epithelium and impact on photoreceptors.

The retinal pigment epithelium (RPE) plays a critical role in the maintenance of the outer retina. RPE cell death or dysfunction drives the pathophysiology of many retinal diseases, but the physiological response of the retina to RPE cell loss is poorly understood, mainly because of the absence of suitable experimental models. Here, we generated a transgenic mouse in which an inducible Cre recombinase is expressed exclusively in the RPE under the control of the monocarboxylate transporter 3 gene promoter (RPE(CreER)). This was crossed with a transgenic mouse harboring a diphtheria toxin A (DTA) chain gene rendered transcriptionally silent by a floxed stop sequence. We show that activation of DTA in the double transgenic mouse (RPE(CreER)/DTA) led to 60-80% RPE cell death, with surviving cells maintaining the integrity of the monolayer by increasing their size. Despite the apparent morphological normality of the enlarged RPE cells in the RPE(CreER)/DTA mice, functional analysis revealed significant deficits on electroretinography, and retinal histopathology showed regions of photoreceptor rosetting and degeneration although with retention of a normal vascular network. Our study reveals that whilst the RPE monolayer has a remarkable intrinsic capacity to cope with cellular attrition, specific aspects of RPE multifunctionality essential for photoreceptor survival are compromised. The RPE(CreER)/DTA mouse offers advantages over models that employ chemical or mechanical strategies to kill RPE cells, and should be useful for the development and evaluation of RPE-based therapies, such as stem cell transplantation.

A novel vertebrate eye using both refractive and reflective optics.

Sunlight is attenuated rapidly in the ocean, resulting in little visually useful light reaching deeper than approximately 1000 m in even the clearest water. To maximize sensitivity to the relatively brighter downwelling sunlight, to view the silhouette of animals above them, and to increase the binocular overlap of their eyes, many mesopelagic animals have developed upward-pointing tubular eyes. However, these sacrifice the ability to detect bioluminescent and reflective objects in other directions. Thus, some mesopelagic fish with tubular eyes extend their visual fields laterally and/or ventrally by lensless ocular diverticula, which are thought to provide unfocused images, allowing only simple detection of objects, with little spatial resolution. Here, we show that a medial mirror within the ventrally facing ocular diverticulum of the spookfish, Dolichopteryx longipes, consisting of a multilayer stack derived from a retinal tapetum, is used to reflect light onto a lateral retina. The reflective plates are not orientated parallel to the surface of the mirror. Instead, plate angles change progressively around the mirror, and computer modeling indicates that this provides a well-focused image. This is the first report of an ocular image being formed in a vertebrate eye by a mirror.

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.

The eyes of suckermouth armoured catfish (Loricariidae, subfamily Hypostomus): pupil response, lenticular longitudinal spherical aberration and retinal topography.

The dilated, round pupils of a species of suckermouth armoured catfish (Liposarcus pardalis) constrict slowly on illumination (over 35-40 min) to form crescent-shaped apertures. Ray tracing of He-Ne laser beams shows that the lenses of a related species (Pterygoplichthys etentaculus), which also has a crescent-shaped pupil, are well corrected for longitudinal spherical aberration, suggesting that the primary purpose of the irregular pupil in armoured catfish is not to correct such aberration. It is suggested that the iris operculum may serve to camouflage the pupil of these substrate-dwelling species. An examination of the catfish retina shows the photoreceptors to be exclusively single cones interspersed with elongate rods and demonstrates the presence of multiple optic nerve head papillae. Two areas of high ganglion cell density, each side of a vertically oriented falciform process, provide increased spatial resolving power along the axes examining the substrate in front of and behind the animal.

A comparative study of stimulus-specific pupil responses in the domestic fowl (Gallus gallus domesticus) and the human.

Pupil responses triggered by specific stimulus attributes such as spatial structure, colour and light flux changes were measured in eight domestic fowl. Comparative experiments were also carried out in human subjects. The results were unexpected in that large increments in light flux caused only small constrictions of the pupil. A red stimulus, on the other hand, caused a relatively large pupil response, but a green stimulus was less effective. This finding suggests that the size of the pupil, apart from being controlled by well-described pretectal pathways that mediate luminance responses, is also subject to other inputs. The pupil response in the domestic fowl may therefore make an effective quantitative indicator of things of significance to the animal. In some ways these observations are similar to other findings in primates in that the processing of stimulus attributes such as colour and structure that are not normally associated with the light reflex pathway can cause a pupil response. The fowl pupil does however respond very fast when large light flux changes or red stimuli are involved. Results obtained with sinusoidally modulated light flux changes reveal a short response latency of 105 ms (SD=8.3). In contrast, human responses measured for similar stimulus conditions reveal a latency of 434 ms (SD=36). The speed of pupil response in the fowl is significantly higher than in humans, but the response amplitude is usually small. Another interesting observation is the lack of sustained response to changes in ambient illumination. These findings suggest that the input to the pupilloconstrictor neurones in the fowl consists largely of transient neurones with little sustained component.