Ontogenetic changes in retinal structure and visual acuity: a comparative study of coral-reef teleosts with differing post-settlement lifestyles

Changes in retinal structure during settlement were investigated in four species of tropical reef-associated teleost fishes with differing periods of planktonic duration and post-settlement lifestyles. They were: Apogon doederleini (Apogonidae), a nocturnal planktivore; Stethojulis strigiventer (Labridae), a diurnal microcarnivore; Upeneus tragula (Mullidae), a carnivore which uses chin barbels to disturb invertebrates from the sediment; and Pomacentrus moluccensis (Pomacentridae), a diurnal herbivorous planktivore. The densities of cones, rods, cells in the inner nuclear layer and cells in the ganglion cell layer were estimated in a size range of each species. Visual acuity was calculated using cone densities and lens diameter. The ontogenetic sequence of changes in cell density was similar in all species but interspecific variation in the timing and rates of change was found and could be related to lifestyle. For example, cone densities decreased and rod densities increased most rapidly in the nocturnal species, A. doederleini, during settlement. In contrast, high cone densities were maintained in the species adopting a diurnal lifestyle. Theoretical visual acuity was found to increase rapidly as lens size increased, but was similar for all species at similar lens sizes, indicating the importance of larger eye size as a means for improving resolution during early stages of eye growth. It was concluded that for the species undergoing abrupt lifestyle changes at settlement, structural re-organisation of the retina is important for the survival of the fish as they leave the pelagic environment and take up their reef-associated lifestyle.     

Multifocal lenses compensate for chromatic defocus in vertebrate eyes

The focal length of the vertebrate eye is a function of wavelength, i.e. the eye suffers from longitudinal chromatic aberration. Chromatic defocus is a particularly severe problem in eyes with high light-gathering ability, since depth of field is small due to a pupillary opening that is large in relation to the focal length of the eye. Calculations show that in such eyes only a narrow spectral band of light can be in focus on the retina. For the major part of the visual spectrum, spatial resolution should be limited by the optics of the eye and far lower than the resolving power achievable by the retinal cone photoreceptor mosaic. To solve this problem, fishes with irises unresponsive to light have developed lenses with multiple focal lengths. Well-focused images are created at the wavelengths of maximum absorbance of all spectral cone types. Multifocal lenses also appear to be present in some terrestrial species. In eyes with mobile irises, multifocal lenses are correlated with pupil shapes that allow all zones of the lens, with different refractive powers, to participate in the imaging process, irrespective of the state of pupil constriction. Accepted: 6 November 1998     

Colour vision and visual ecology of the blue-spotted maskray, <Emphasis Type="Italic">Dasyatis kuhlii</Emphasis> Müller &; Henle, 1814

Relatively little is known about the physical structure and ecological adaptations of elasmobranch sensory systems. In particular, elasmobranch vision has been poorly studied compared to the other senses. Virtually nothing is known about whether elasmobranchs possess multiple cone types, and therefore the potential for colour vision, or how the spectral tuning of their visual pigments is adapted to their different lifestyles. In this study, we measured the spectral absorption of the rod and cone visual pigments of the blue-spotted maskray, Dasyatis kuhlii, using microspectrophotometry. D. kuhlii possesses a rod visual pigment with a wavelength of maximum absorbance (λ_max) at 497 nm and three spectrally distinct cone types with λ_max values at 476, 498 and 552 nm. Measurements of the spectral transmittance of the ocular media reveal that wavelengths below 380 nm do not reach the retina, indicating that D. kuhlii is relatively insensitive to ultraviolet radiation. Topographic analysis of retinal ganglion cell distribution reveals an area of increased neuronal density in the dorsal retina. Based on peak cell densities and using measurements of lens focal length made using laser ray tracing and sections of frozen eyes, the estimated spatial resolving power of D. kuhlii is 4.10 cycles per degree.     

Modelling the visual world of a velvet worm

In many animal phyla, eyes are small and provide only low-resolution vision for general orientation in the environment. Because these primitive eyes rarely have a defined image plane, traditional visual-optics principles cannot be applied. To assess the functional capacity of such eyes we have developed modelling principles based on ray tracing in 3D reconstructions of eye morphology, where refraction on the way to the photoreceptors and absorption in the photopigment are calculated incrementally for ray bundles from all angles within the visual field. From the ray tracing, we calculate the complete angular acceptance function of each photoreceptor in the eye, revealing the visual acuity for all parts of the visual field. We then use this information to generate visual filters that can be applied to high resolution images or videos to convert them to accurate representations of the spatial information seen by the animal. The method is here applied to the 0.1 mm eyes of the velvet worm Euperipatoides rowelli (Onychophora). These eyes of these terrestrial invertebrates consist of a curved cornea covering an irregular but optically homogeneous lens directly joining a retina packed with photoreceptive rhabdoms. 3D reconstruction from histological sections revealed an asymmetric eye, where the retina is deeper in the forward-pointing direction. The calculated visual acuity also reveals performance differences across the visual field, with a maximum acuity of about 0.11 cycles/deg in the forward direction despite laterally pointing eyes. The results agree with previous behavioural measurements of visual acuity, and suggest that velvet worm vision is adequate for orientation and positioning within the habitat.     

Vision in elasmobranchs and their relatives: 21st century advances

This review identifies a number of exciting new developments in the understanding of vision in cartilaginous fishes that have been made since the turn of the century. These include the results of studies on various aspects of the visual system including eye size, visual fields, eye design and the optical system, retinal topography and spatial resolving power, visual pigments, spectral sensitivity and the potential for colour vision. A number of these studies have covered a broad range of species, thereby providing valuable information on how the visual systems of these fishes are adapted to different environmental conditions. For example, oceanic and deep-sea sharks have the largest eyes amongst elasmobranchs and presumably rely more heavily on vision than coastal and benthic species, while interspecific variation in the ratio of rod and cone photoreceptors, the topographic distribution of the photoreceptors and retinal ganglion cells in the retina and the spatial resolving power of the eye all appear to be closely related to differences in habitat and lifestyle. Multiple, spectrally distinct cone photoreceptor visual pigments have been found in some batoid species, raising the possibility that at least some elasmobranchs are capable of seeing colour, and there is some evidence that multiple cone visual pigments may also be present in holocephalans. In contrast, sharks appear to have only one cone visual pigment. There is evidence that ontogenetic changes in the visual system, such as changes in the spectral transmission properties of the lens, lens shape, focal ratio, visual pigments and spatial resolving power, allow elasmobranchs to adapt to environmental changes imposed by habitat shifts and niche expansion. There are, however, many aspects of vision in these fishes that are not well understood, particularly in the holocephalans. Therefore, this review also serves to highlight and stimulate new research in areas that still require significant attention.     

Growth of the teleost eye: novel solutions to complex constraints

Synopsis The cichlid fish, Haplochromis burtoni, is highly dependent on vision for survival in its natural habitat. As is true of most teleost fishes, the eyes continue to grow throughout life without any obvious changes in visual capability. In H. burtoni, for example, retinal area may increase by 27 × in just 6 months. During growth, there is no obvious change in the visual sensitivity, visual acuity or lens quality which must all be appropriate for the enlarging eye. This requires that during growth competing constraints be met. For example, to maintain visual acuity, the number of ganglion cells per visual angle subtended on the retina must remain the same as must the convergence ratio of the cones onto those ganglion cells. In contrast, to maintain visual sensitivity, the number of rod photoreceptors per unit retinal area must remain the same. These requirements are in conflict since a larger eye may preserve acuity with fewer cells per unit area in a larger retina. In addition, the lens properties must remain the same as the animal increases in size so that the image available is of similar quality throughout life. Experiments have been performed to reveal the adaptations during growth which allow the fish to preserve its image of the world throughout life.     

Human Retinal Progenitor Cell Transplantation Preserves Vision

Cell transplantation is a potential therapeutic strategy for retinal degenerative diseases involving the loss of photoreceptors. However, it faces challenges to clinical translation due to safety concerns and a limited supply of cells. Human retinal progenitor cells (hRPCs) from fetal neural retina are expandable in vitro and maintain an undifferentiated state. This study aimed to investigate the therapeutic potential of hRPCs transplanted into a Royal College of Surgeons (RCS) rat model of retinal degeneration. At 12 weeks, optokinetic response showed that hRPC-grafted eyes had significantly superior visual acuity compared with vehicle-treated eyes. Histological evaluation of outer nuclear layer (ONL) characteristics such as ONL thickness, spread distance, and cell count demonstrated a significantly greater preservation of the ONL in hRPC-treated eyes compared with both vehicle-treated and control eyes. The transplanted hRPCs arrested visual decline over time in the RCS rat and rescued retinal morphology, demonstrating their potential as a therapy for retinal diseases. We suggest that the preservation of visual acuity was likely achieved through host photoreceptor rescue. We found that hRPC transplantation into the subretinal space of RCS rats was well tolerated, with no adverse effects such as tumor formation noted at 12 weeks after treatment.     

From optics to attention: visual perception in barn owls

Barn owls are nocturnal predators which have evolved specific sensory and morphological adaptations to a life in dim light. Here, some of the most fundamental properties of spatial vision in barn owls are reviewed. The eye with its tubular shape is rigidly integrated in the skull so that eye movements are very much restricted. The eyes are oriented frontally, allowing for a large binocular overlap. Accommodation, but not pupil dilation, is coupled between the two eyes. The retina is rod dominated and lacks a visible fovea. Retinal ganglion cells form a marked region of highest density that extends to a horizontally oriented visual streak. Behavioural visual acuity and contrast sensitivity are poor, although the optical quality of the ocular media is excellent. A low f-number allows high image quality at low light levels. Vernier acuity was found to be a hyperacute percept. Owls have global stereopsis with hyperacute stereo acuity thresholds. Neurons of the visual Wulst are sensitive to binocular disparities. Orientation based saliency was demonstrated in a visual-search experiment, and higher cognitive abilities were shown when the owl’s were able to use illusory contours for object discrimination.     

Photoreceptors and photopigments in a subterranean rodent,the pocket gopher (<Emphasis Type="Italic">Thomomys bottae</Emphasis>)

Pocket gophers (Thomomys bottae) are rodents that spend much of their lives in near-lightless subterranean burrows. The visual adaptations associated with this extreme environment were investigated by making anatomical observations of retinal organization and by recording retinal responses to photic stimulation. The size of the eye is within the normal range for rodents, the lens transmits light well down into the ultraviolet, and the retina conforms to the normal mammalian plan. Electroretinogram recording revealed the presence of three types of photopigments, a rod pigment with a spectral peak of about 495 nm and two types of cone pigment with respective peak values of about 367 nm (UV) and 505 nm (medium-wavelength sensitive). Both in terms of responsivity to lights varying in temporal frequency and in response recovery following intense light adaptation, the cone responses of the pocket gopher are similar to those of other rodents. Labeling experiments indicate an abundance of cones that reach densities in excess of 30,000 mm^–2. Cones containing UV opsin are found throughout the retina, but those containing medium-wavelength sensitive opsin are mostly restricted to the dorsal retina where coexpression of the two photopigments is apparently the rule. Rod densities are lower than those typical for nocturnal mammals.     

Low-Vision Rehabilitation by Means of MP-1 Biofeedback Examination in Patients with Different Macular Diseases: A Pilot Study

Macular disease is one of the main causes of visual impairment. We studied the efficacy of low-vision rehabilitation by means of MP-1 biofeedback examination in patients with different macular disease. Five patients were enrolled (3 female and 2 male, mean age 53.8 years) and a total of 9 eyes was examined: 2 eyes with vitelliform dystrophy, 1 with a post-traumatic macular scar, 2 with Stargardt disease, 2 with myopic macular degeneration, 2 with cone dystrophy. All the patients underwent the following tests: visual acuity, reading speed, fixation test, MP-1 microperimetry. Low-vision rehabilitation, which lasted 10 weeks, consisted of 10 training sessions of 10 min for each eye, performed once a week using the MP-1 biofeedback examination. Statistical analysis was performed using Student’s t-test. p values less than 0.05 were considered statistically significant. After training all patients displayed an improvement in visual acuity, fixation behaviour, retinal sensitivity and reading speed. Fixation behaviour within the 2° diameter circle improved and was statistically significant for reading speed (p = 0.01). Reading speed improved from a mean value of 64.3 to 92 words/min. Our results show that audio feedback can, by increasing attentional modulation, help the brain to fix the final preferred retinal locus. Audio feedback facilitates stimuli transmission between intraretinal neurons as well as between the retina and brain, which is where the highest level of stimuli processing occurs, thereby probably supporting a “remapping phenomenon”.     

Guanine and its retinal distribution in the tapetum of the bigeye tuna,thunnus obesus

The eye of the bigeye tuna (Thunnus obesus) contains a retinal tapetum composed of guanine. The total amount of the guanine in one eye of the fish (SL=120 cm) was about 88.6 mg. The mean guanine content of the tapetum was approximately 1.25 mg/cm² of the retinal surface. The highest content of guanine (2.15 mg/cm²) was observed only in the ventro-temporal part of the retina. To distinguish this area from the rest of the eye, we suggested the term ‘locus tapetalis’ for it. The visual accommodation system clearly indicated that the visual axis of the fish is upper-forward and the resulting retinal area for acute vision was suggested to be in the ventro-temporal retina. We discussed that the area centralis of the bigeye tuna may have two functions: to guarantee high visual acuity and to allow for high photo-sensitivity in dim light vision.     

Ocular changes accompanying eye loss in the spider family uloboridae

In uloborid spiders, eye loss is accompanied by increased visual angles, optical material investment, and potential visual acuity of the retained eyes. Relative to carapace volume, the six-eyed Hyptiotes cavatus and two four-eyed Miagrammopes species have greater retinal hemisphere areas and lens volumes than do the eight-eyed uloborids Waitkera waitkerensis, Uloborus glomosus, and Octonoba sinensis. In Waitkera, in which the eyes have little visual overlap, and in Miagrammopes, in which eye loss simplifies the spiders' patterns of visual overlap, increased retinal cell density enhances potential visual acuity. However, this occurs at the expense of potential retinal cell sensitivity.     

Regional variations in the outer retina of atherinomorpha (Beloniformes,Atheriniformes, Cyprinodontiformes: Teleostei): photoreceptors,cone patterns,and cone densities

The outer retinae of adults of 13 atherinomorph species, representing nine different families, were examined by both light and electron microscopy. The retinae were investigated with respect to photoreceptor types, cone densities, and cone patterns. All data were composed to eye maps. This procedure allows an interspecific comparison of the regional differences within the outer retina among these shallow-water fish. Furthermore, for a more detailed pattern analysis nitro-blue tetrazolium chloride- (NBT)-stainings in the retina of Melanotaenia maccullochi are presented. Apart from rods, eight morphologically different cone types could be identified: short, intermediate, and long single cones, double cones (equal and unequal), triple cones (triangular and linear), and in Ameca splendens one quadruple cone. Dimensions and occurrence of photoreceptors vary among the respective species and within the retinal regions. In the light-adapted state, the cones are arranged in highly ordered mosaics. Five different cone tessellation types were found: row patterns, twisted row patterns, square patterns, pentagonal patterns, and, exclusively in Belone belone, a hexagonal pattern. In Melanotaenia maccullochi the different spectral photoreceptor classes correspond well with the distribution of morphological photoreceptor classes within the mosaic. Double cone density maxima together with a highly ordered cone arrangement usually occur in the nasal and/or ventral to ventrotemporal retina. In most of the species that were examined these high-density regions are presumed to process visual stimuli from the assumed main directions of vision, which mainly depend on feeding behavior and predator pressure. Our findings are discussed with respect to the variable behavioral and visual ecology and phylogeny of the respective species.     

Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina

Amyloid precursor protein (APP) is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO) mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT) and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.     

The Development of Vision in the Zebrafish (Danio rerio)

We studied the development and maturation of the visual system by determining when zebrafish begin to see and to move their eyes. This information was correlated with the time courses of the development of the retina, the retinofugal projection, the retinal image, and the extraocular muscles, to obtain an integrated picture of early visual development. Two visual behaviors were monitored over 48–96 hr postfertilization (hpf). The startle response (body twitch) was evoked by an abrupt decrease in light intensity. The optokinetic response (tracking eye movements) was evoked by rotation of a striped drum. Visually evoked startle developed over 68–79 hpf, more than 20 hr after the onset of a touch-evoked startle. It was not seen in eyeless fish, excluding a role for nonretinal light senses. Tracking eye movements developed over 73–80 hpf. They were always in the direction of drum rotation, even when the fish had been light deprived from blastula stage, ruling out a “trial and error” period of learning to track the drum. The image formed by the ocular lens was examined in intact fish made transparent by suppressing the formation of melanin. The eye was initially far sighted and gradually improved, so that by 72 hpf the image plane coincided with the photoreceptor layer. The extraocular muscles assumed their adult configuration between 66 and 72 hpf. Thus, the retinal image and functional extraocular muscles appeared nearly simultaneously with the onset of tracking eye movements and probably represent the last events in the construction of this behavior.     

Immunohistochemical evidence for multiple photosystems in box jellyfish

Cubomedusae (box jellyfish) possess a remarkable visual system with 24 eyes distributed in four sensory structures termed rhopalia. Each rhopalium is equipped with six eyes: two pairs of pigment cup eyes and two unpaired lens eyes. Each eye type probably captures specific features of the visual environment. To investigate whether multiple types of photoreceptor cells are present in the rhopalium, and whether the different eye types possess different types of photoreceptors, we have used immunohistochemistry with a range of vertebrate opsin antibodies to label the photoreceptors, and electroretinograms (ERG) to determine their spectral sensitivity. All photoreceptor cells of the two lens eyes of the box jellyfish Tripedalia cystophora and Carybdea marsupialis displayed immunoreactivity for an antibody directed against the zebrafish ultraviolet (UV) opsin, but not against any of eight other rhodopsin or cone opsin antibodies tested. In neither of the two species were the pigment cup eyes immunoreactive for any of the opsin antibodies. ERG analysis of the Carybdea lower lens eyes demonstrated a single spectral sensitivity maximum at 485 nm suggesting the presence of a single opsin type. Our data demonstrate that the lens eyes of box jellyfish utilize a single opsin and are thus color-blind, and that there is probably a different photopigment in the pigment cup eyes. The results support our hypothesis that the lens eyes and the pigment cup eyes of box jellyfish are involved in different and specific visual tasks.     

The lens controls cell survival in the retina: Evidence from the blind cavefish Astyanax

The lens influences retinal growth and differentiation during vertebrate eye development but the mechanisms are not understood. The role of the lens in retinal growth and development was studied in the teleost Astyanax mexicanus, which has eyed surface-dwelling (surface fish) and blind cave-dwelling (cavefish) forms. A lens and laminated retina initially develop in cavefish embryos, but the lens dies by apoptosis. The cavefish retina is subsequently disorganized, apoptotic cells appear, the photoreceptor layer degenerates, and retinal growth is arrested. We show here by PCNA, BrdU, and TUNEL labeling that cell proliferation continues in the adult cavefish retina but the newly born cells are removed by apoptosis. Surface fish to cavefish lens transplantation, which restores retinal growth and rod cell differentiation, abolished apoptosis in the retina but not in the RPE. Surface fish lens deletion did not cause apoptosis in the surface fish retina or affect RPE differentiation. Neither lens transplantation in cavefish nor lens deletion in surface fish affected retinal cell proliferation. We conclude that the lens acts in concert with another optic component, possibly the RPE, to promote retinal cell survival. Accordingly, deficiency in both optic structures may lead to eye degeneration in cavefish.     

Ultrastructure of trypan blue induced ocular defects: I. Retina and lens

The histological and cytological basis of trypan blue-induced ocular defects were studied using scanning and transmission electron microscopy. Microphthalmic and anophthalmic eyes of 16-day rat fetuses were utilized from dams exposed to a teratogenic dose of trypan blue. Retinal and lenticular anlagen were specifically examined for architectural and cellular changes. Nearly all severely abnormal eyes showed no evidence of retina development: Of 41 such eyes, only two retinal rudiments were observed. Those eyes with mild microphthalmia always demonstrated retinae although architectural changes were present. In every abnormal eye, some degree of lenticular morphogenesis was always present. Lenses were small, displaced in the eye field, and arrested at the lens vesicle stage. Lens cells were markedly undifferentiated and thus lacked most of the cytological features normally present at this developmental stage. Neither retinal nor lenticular rudiments were necrotic despite major architectural and cytological disturbances. The data offer three conclusions: First, the absence of necrosis suggests that trypan blue causes developmental arrest in this eye model; second, absence of retinae is most likely due to primary failure of optic vesicle development; third, lack of lens differentiation is attributed to absence of the retina, the primary lens inducer.     

Fixational Eye Movements in the Earliest Stage of Metazoan Evolution

All known photoreceptor cells adapt to constant light stimuli, fading the retinal image when exposed to an immobile visual scene. Counter strategies are therefore necessary to prevent blindness, and in mammals this is accomplished by fixational eye movements. Cubomedusae occupy a key position for understanding the evolution of complex visual systems and their eyes are assumedly subject to the same adaptive problems as the vertebrate eye, but lack motor control of their visual system. The morphology of the visual system of cubomedusae ensures a constant orientation of the eyes and a clear division of the visual field, but thereby also a constant retinal image when exposed to stationary visual scenes. Here we show that bell contractions used for swimming in the medusae refresh the retinal image in the upper lens eye of Tripedalia cystophora. This strongly suggests that strategies comparable to fixational eye movements have evolved at the earliest metazoan stage to compensate for the intrinsic property of the photoreceptors. Since the timing and amplitude of the rhopalial movements concur with the spatial and temporal resolution of the eye it circumvents the need for post processing in the central nervous system to remove image blur.     

Vertebrate features revealed in the rudimentary eye of the Pacific hagfish (Eptatretus stoutii)

Hagfish eyes are markedly basic compared to the eyes of other vertebrates, lacking a pigmented epithelium, a lens and a retinal architecture built of three cell layers: the photoreceptors, interneurons and ganglion cells. Concomitant with hagfish belonging to the earliest-branching vertebrate group (the jawless Agnathans), this lack of derived characters has prompted competing interpretations that hagfish eyes represent either a transitional form in the early evolution of vertebrate vision, or a regression from a previously elaborate organ. Here, we show the hagfish retina is not extensively degenerating during its ontogeny, but instead grows throughout life via a recognizable PAX6+ ciliary marginal zone. The retina has a distinct layer of photoreceptor cells that appear to homogeneously express a single opsin of the RH1 rod opsin class. The epithelium that encompasses these photoreceptors is striking because it lacks the melanin pigment that is universally associated with animal vision; notwithstanding, we suggest this epithelium is a homologue of gnathosome retinal pigment epithelium (RPE) based on its robust expression of RPE65 and its engulfment of photoreceptor outer segments. We infer that the hagfish retina is not entirely rudimentary in its wiring, despite lacking a morphologically distinct layer of interneurons: multiple populations of cells exist in the hagfish inner retina and subsets of these express markers of vertebrate retinal interneurons. Overall, these data clarify Agnathan retinal homologies, reveal characters that now appear to be ubiquitous across the eyes of vertebrates, and refine interpretations of early vertebrate visual system evolution.