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The spatial resolution capacity of human foveal retina.

An image on the retina of a human eye enters the visual system through an array of photoreceptors that sets the boundaries on the spatial detail available for neural representation. In order to investigate the extent to which the input spatial detail is preserved by the human neural system, we compare the anatomical spatial limits as determined by the Nyquist frequency, the highest spatial frequency reconstructable from the cone array, and measures of human acuity, the minimum angle resolvable. We find that the anatomical Nyquist limits determined along the temporal horizontal meridian of a well-studied human retina (Curcio, Sloan, Packer, Hendrickson & Kalina, 1987b) offer a reasonable prediction of human acuity within the retinal region extending from slightly off the exact foveal center to about 2.0 deg of retinal eccentricity. However, we find a narrow peak of anatomical resolution at the foveal center where the acuity appears to be overestimated by cone spacing.

Adult↗

The structure and development of the rat retina: an immunofluorescence microscopical study using antibodies specific for intermediate filament proteins.

Rat retina structure was studied between embryonic day 14 and adult with antibodies specific for vimentin, glial fibrillary acidic protein (GFA) and the proteins of the neurofilament triplet. Vimentin could be detected in radial processes throughout the retina at all stages studied. These processes are believed to correspond, in the developing retina, to ventriculocytes, and in the mature retina to Müller cells. They could not normally be stained with any of the other intermediate filament antibodies employed here. We did find, however, that some older albino rats possessed GFA staining in addition to vimentin in these processes. Since we never saw such staining in the retinae of mature non-albino rats, and the retinae of older albino rats often showed signs of degeneration, we concluded that such GFA expression was most likely pathological. Neurofilament protein-positive processes were first detectable at embryonic day 15 1/2 in the inner regions of the retina, and corresponded to the axons of retinal ganglion cells. Such processes were equivalently displayed with antibodies to 68 K and 145 K protein, but were negative with 200 K protein. Some 68 K and 145 K positive fibers could also be decorated with vimentin antibody at this stage, though at later stages this was not the case. At later development stages more 68 K and 145 K neurofilament positive processes appeared, and after the first post-natal week progressively more of such processes became in addition 200 K positive, so that almost all neurofilament positive fibers in the adult stained for all three proteins. Such fibers, in the mature retina corresponded to 68 K and 145 K positive optic nerve fibers, and the processes of neurones in the inner plexiform layer. All fibers in the mature optic nerve fiber layer, but not all of those in the inner plexiform layer were stainable with 200 K antibodies. At 4 days post-natal we were able to detect 68 K and 145 K protein positive profiles in the outer regions of the developing retina, the prospective outer plexiform layer. Such profiles were always in addition vimentin positive, but negative for 200 K protein. During further development such profiles became ordered into a well defined layer and from about post-natal day 13 all of them began to acquire 200 K protein. They could be identified as the processes of horizontal cells. They continued to express vimentin in addition to the three triplet proteins in the adult, a so far unprecedented situation. We were able to detect neurofilament staining in the mature retina only in the above described regions, the inner and outer nuclear layer and the photoreceptor processes being completely free of staining. GFA was first detected in short processes adjacent to the inner limiting membrane which penetrated the optic nerve fiber layer. Such profiles were first detectable in the eye of the newborn animal, and were invariably identically stainable with vimentin at this age. These profiles could be stained with both vimentin and GFA at all later stages examined, although GFA staining became very much stronger than vimentin staining in some profiles in the adult. The results presented here are discussed in terms of development of the different retinal cell types.

Age Factors↗

Horizontal cells feed back to cones by shifting the cone calcium-current activation range.

We studied feedback from horizontal cells to cones in isolated goldfish retinae and found that surround stimuli evoke an inward current and a slowly developing outward current. The surround-evoked currents are blocked by the glutamate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) and are, like horizontal cell responses, most effectively evoked by large stimuli. This indicates that the currents are caused by feedback from horizontal cells. The surround-evoked inward current is neither blocked by picrotoxin nor carried by chloride. Instead, it is carried by calcium, and it triggers a slowly developing calcium-dependent chloride current. We were unable to mimick the surround-evoked currents by modulating the extracellular GABA concentration. We conclude that when horizontal cells hyperpolarize they feed back to the cones by shifting the cone calcium-current activation range to more negative potentials. This type of feedback, directly targeted at the calcium current, scarcely influences the membrane potential of the receiving neuron, but effectively modulates its synaptic output.

Animals↗

[Vigabatrin: balancing effectiveness vs. (irreversible) visual field loss as a side effect].

The antiepileptic drug vigabatrin causes an asymptotic concentric contraction of the visual field in 30 to 40% of the patients. The visual field loss seems to be correlated with the cumulative dose of vigabatrin and is not reversible. The cause of this field loss is located in the inner retina (the horizontal and/or amacrine cells). The exact mechanism is still unknown. Though abnormalities in electrophysiology and colour vision are found, regular visual field examination remains the cornerstone in detecting visual field loss. A careful judgement has to be made in individual patients before starting or continuing vigabatrin medication.

4-Aminobutyrate Transaminase↗

The pattern of cone pedicles and horizontal cells in the retina of the European anchovy, Engraulis encrasicolus L. (Engraulididae, Clupeiformes).

We have studied the architecture of polycone pedicles and their postsynaptic horizontal cells in the European anchovy using serial reconstruction by means of thin-sections from the cone outer segments to the outer plexiform layer. Within this layer there is a tesselated arrangement of pedicles in two strata, one made by the long-cone pedicles and one by those of the short-cones. The two pedicle types differ in the architecture of their synaptic sites. The long-cones possess two ribbon clusters corresponding to two bunches of subsynaptic dendrites, while the short-cones have only a single ribbon cluster innervated by a single group of dendrites. In addition, telodendria specifically connect the cone pedicles of neighbouring rows. Among the horizontal cells three classes arranged in separate levels can be distinguished. Serial reconstruction results suggest that first level horizontal cells contact long-cones preferentially. Among bipolar cells with an oval shaped dendritic field another type is found with a rectangular field of polycone-parallel dendritic combs. These findings indicate that the uncommon cone structures of engraulidids, which probably subserve polarization contrast vision, are correlated with a peculiar geometry of the outer plexiform layer.

Animals↗

Glycinergic pathways in the goldfish retina.

Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish has been used to study some anatomical and physiological properties of potentially glycinergic neurons. There are two classes of retinal cells exhibiting high affinity glycine uptake: Aa amacrine cells and I2 interplexiform cells. Aa amacrine cells constitute about 20% of the somas in the amacrine cell layer and send their dendrites to the middle of the inner plexiform layer. There they are both pre- and postsynaptic primarily to other amacrine cells. Photic modulation of glycine uptake indicates that they are probably red-hyperpolarizing/green-depolarizing neurons. I2 interplexiform cells are a newly discovered type of interplexiform cell; in the outer plexiform layer, they receive direct synaptic input from the somas of red-dominated GABAergic H1 horizontal cells and are apparently presynaptic to dendrites of unidentified types of horizontal cells. The connections of I2 interplexiform cells have not been successfully characterized in the inner plexiform layer. These findings extend our knowledge of neurochemically specific pathways in the cyprinid retina and indicate that glycine, like GABA, is a neurotransmitter primarily involved with circuits coding "red" information.

Animals↗

Fine structure of the retina of black bass, Micropterus salmoides (Centrarchidae, Teleostei).

The structure of light- and dark-adapted retina of the black bass, Micropterus salmoides has been studied by light and electron microscopy. This retina lacks blood vessels at all levels. The optic fiber layer is divided into fascicles by the processes of Müller cells and the ganglion cell layer is represented by a single row of voluminous cells. The inner nuclear layer consists of two layers of horizontal cells and bipolar, amacrine and interplexiform cells. In the outer plexiform layer we observed the synaptic terminals of photoreceptor cells, rod spherules and cone pedicles and terminal processes of bipolar and horizontal cells. The spherules have a single synaptic ribbon and the pedicles possess multiple synaptic ribbons. Morphologically, we have identified three types of photoreceptors: rods, single cones and equal double cones which undergo retinomotor movements in response to changes in light conditions. The cones are arranged in a square mosaic whereas the rods are dispersed between the cones.

Animals↗

Peak density and distribution of ganglion cells in the retinae of microchiropteran bats: implications for visual acuity.

We have estimated the total number, distribution and peak density of retinal ganglion cells (RGCs) in retinal wholemounts of several species of microchiropteran (echolocating) bats. The estimates are based on counts of Nissl-stained, presumed RGCs. The total number of presumed RGCs varies among the species: from about 4,500 in Rhinolophus rouxi to about 120,000 in Macroderma gigas. In addition, in two species (Nyctophilus gouldi and M. gigas), the estimates are based on counts of positively identified RGCs retrogradely labelled with the enzyme horseradish peroxidase injected into the retinorecipient nuclei. In these two species, the numbers and distributions of retrogradely labelled RGCs and Nissl-stained presumed RGCs are very similar. In all six species studied, the peak-density regions of presumed (or positively identified) RGCs are located in the inferotemporal retinae, and the RGC isodensity lines tend to be horizontally elongated. However, the RGC densities in the high-density regions are only 2-4 times greater than those in the low-density regions in the superior retinae. The somal sizes of RGCs vary from 5 to 16 micron in diameter and are unimodally distributed. There is no indication of the existence of distinct morphological classes of RGCs. The axial lengths of microchiropteran eyes vary from 1.8 mm in R. rouxi to 7.0 mm in M. gigas. For all species the posterior nodal distance (PND) was assumed to be 0.52 of the axial length of the eye. This assumption is based on the analysis of published data concerning schematic eyes of nocturnal vertebrates. These derived values of the PNDs allowed us to calculate the retinal magnification factors and the number of RGCs per degree of visual angle. From these, the upper limits of visual acuity were derived on the basis of the assumptions of the sampling theorem. The estimated upper limits of visual acuity of the six species of echolocating bats vary from about 0.35 cycles/degree in R. rouxi to about 2 cycles/degree in M. gigas. This range is quite similar to the range of visual acuities in murid rodents.

Animals↗

Neural and optical limits to visual performance in myopia.

We investigated the relative importance of neural and optical limitations to visual performance in myopia. A number of visual performance measures were made on all or subsets of 121 eyes of emmetropic and myopic volunteers aged 17-35 years. These tests included visual measures that are mainly neurally limited (spatial summation out to +/-30 degrees in the horizontal visual field and resolution acuity out to +/-10 degrees in the horizontal visual field) and central ocular aberrations. We found that myopia affected the neurally limited tests, but had little effect on central higher order aberration. The critical area for spatial summation increased in the temporal visual field at 0.03 log units/dioptre of myopia. Resolution acuity decreased at approximately 0.012 log units/dioptre of myopia. Losses of visual function were slightly greater in the temporal than in the nasal visual field. The observed visual deficit in myopia can be explained by either global retinal expansion with some post-receptor loss (e.g. ganglion cell death) or a posterior polar expansion in which the point about which expansion occurs is near the centre of the previously emmetropic globe.

Adolescent↗

Parametric representation of Stiles-Crawford functions: normal variation of peak location and directionality.

Evidence suggests that the psychophysically determined Stiles-Crawford effect of the first kind (SCE) reflects waveguide properties of human photoreceptors. The peak of the SCE data set is assumed to reflect the principal alignment tendencies, and the spread (e.g., rho value, the curvature or width at half-height) is assumed to reflect the directionality (i.e., interreceptor differences in alignment) of the population of photoreceptors being tested. As such, disruption of the normal SCE can be used and/or has been used (1) to document early natural history of retinal pathology involving the photoreceptors, (2) to provide a firm rationale for therapeutic intervention, and (3) to provide a method for monitoring therapies designed to alter the natural course of retinal-disease processes. We report large-sample norms for foveal SCE peak location and spread (horizontal peak location, nasal 0.51 +/- 0.72, horizontal rho value 0.047 +/- 0.013, vertical peak location, superior 0.20 +/- 0.64, vertical rho value 0.053 +/- 0.012), compare these norms with values determined in other laboratories, and discuss the various mathematical forms used for the empirical description of SCE data sets.

Adult↗

The epithelial sodium channel (ENaC) in rodent retina, ontogeny and molecular identity.

PURPOSE: To assess the appearance of the epithelial sodium channels (ENaC) during retinal development and establish its molecular identity. METHODS: Photoreceptors were isolated by horizontal sectioning of rat retina with a vibratome series 1000. Intact retina and isolated photoreceptors were analyzed for the developmental appearance of ENaC using the Polymerase Chain Reaction (PCR) technique. Immunofluorescence was conducted with the aid of an antibody raised against the 14 amino acids peptide QGLGKGDKREEQGL, corresponding to the N-terminal region (44-58 aa) of alpha ENaC. RESULTS: ENaC message was present in rat retina photoreceptors, isolated just one day after birth. The bipolar and ganglion cell layers, separated from whole retina by vibratome, also contained the ENaC message. The partial sequence of the photoreceptor ENaC (496 base) exhibited one hundred percent homology with the channel from rat known sources. Immunochemistry revealed that only the outer nuclear layer was positive for the ENaC in one-day-old rat; the inner segment became immunopositive at the age of 9 days. CONCLUSION: The ENaC is present in the retina and visible soon after birth. These observations suggest that ENaC may prove to have physiological importance in the retina but until now its function is unknown.

Amino Acid Sequence↗

The effect of horizontal-plane environment on the development of binocular receptive fields of cells in cat visual cortex.

1. The different perception of vertical in the two eyes (Helmholtz, 1864) was interpreted as an adaptation of cortical binocular receptive fields to the bias distribution of orientation disparity in the visual environment resulting from the relative frequency of contours in horizontal planes below eye level (ground, table) compared to other orientations in space.2. Kittens were reared in environments where visible contours were confined to a horizontal plane which was the floor for two kittens and the ceiling for two other kittens. The floor tended to produce negative, the ceiling positive, orientation disparities. In either case, the disparities were maximal about the vertical retinal meridians and zero at the horizontal meridian. The preferred stimulus orientations of binocular neurones in area 17 of the visual cortex were determined at 3-4 months age in these four kittens and in seven normal cats for control. Automatic stimulus variation, quantitative analysis, and eye drift correction were used.3. In the ;floor cats' neurones with near-vertical orientations showed a mean interocular angle between the preferred orientations of -8.7 degrees relative to neurones with near-horizontal orientations; in the ;ceiling cats', the angle was +2.8 degrees ; in the normal cats it was -0.4 degrees .4. Since these angles are independent of the alignment of the eyes, the difference between floor cats and ceiling cats reflects different functional connexions at cortical level. This indicates that the orientations of the developing receptive fields can be modified by visual experience.5. These observations in kittens suggest that the perceptual difference between the eyes in man is also caused by early visual experience.

Action Potentials↗

Distribution of photoreceptor types in the retina of a marsupial, the tammar wallaby (Macropus eugenii).

Mammalian retinae generally contain low numbers of short-wavelength-sensitive cones (S-cones) and higher numbers of middle- to long-wavelength-sensitive cones (M-cones). Some recent studies found topographic differences between the different photoreceptor types and in some instances between photoreceptors and ganglion cells. To investigate this question further, we constructed topographical maps of the different photoreceptors found in an Australian marsupial, the tammar wallaby. We used two polyclonal antibodies that have been shown to label S-cones (JH455) or M-cones (JH492) in a range of mammals. In the tammar wallaby, the antisera clearly distinguish two cone types. JH455 recognizes a small subset of cones (S-cones) with a density of less than 500 cells/mm2 in the ventral retina. Their density increases towards the dorsal retina to about 1600-2000 cells/mm2. JH492 recognizes all remaining cones (M-cones), but also faintly labels most cone cells recognized by JH455. The distribution of M-cones, unlike that of the S-cones, shows a clear horizontal streak of high cell density through the central retina, just like the ganglion cells. Unlike the ganglion cells, however, the M-cones do not peak in the temporal retina but show a very broad peak (12,000-18,000 cells/mm2) in the central or even slightly nasal retina. Based on our findings, the retina of the tammar can be divided into three distinct regions: firstly, the dorsal retina, which has a low ganglion and low cone cell density but a high percentage of S-cones (30%), is thought to provide good spectral sensitivity; secondly, the central horizontal band of retina, which has a high ganglion and high cone cell density and therefore provides good spatial resolution; and thirdly, the ventral retina, which has a low ganglion cell but high cone cell density with few S-cones (5%) and is therefore thought to have a high contrast sensitivity but low acuity.

Animals↗

Taurine and GABA in the rat retina during postnatal development.

The content of taurine and the immunocytochemical localization of taurine and gamma-aminobutyric acid (GABA) in the rat retina during postnatal development are described. The rat retina is immature at birth; about two-thirds of the cells are undifferentiated neuroblasts, and the taurine content per retina is approximately one-seventh of the adult value. Shortly after weaning the adult morphology and taurine content are attained. Expression of taurine immunoreactivity (taurine-IR) accompanies differentiation; in some cell types (ganglion and horizontal cells) this expression is transient, while in others (photoreceptors, bipolar, and a subpopulation of amacrine cells) it persists into the adult state. At birth, taurine-IR is localized mainly in cells in the position of ganglion cells, especially in their axons within the nerve fiber layer. This reactivity is soon lost from the somata, and disappears from the axons by 10 days of age. At 2 days of age, taurine-IR appeared additionally in somata of amacrine cells flanking the forerunner of the inner plexiform layer, and in growth cone-like processes of photoreceptors. At day 6, taurine-IR was marked in photoreceptor cell inner and outer segments, and in horizontal cells and their lateral processes. Taurine-IR was lost from horizontal cells and most amacrine cells around day 10, and appeared in bipolar cells, where it remained, with that in photoreceptors, into adulthood. Particularly striking was taurine-IR in large synaptic terminal-like processes close to the ganglion cell layer which were first seen around day 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The topography of magnocellular projecting ganglion cells (M-ganglion cells) in the primate retina.

The projection from the retina to the dorsal lateral geniculate nucleus in the primate arises from two morphologically distinct types of ganglion cells. The P-ganglion cells project to the parvocellular layers, the M-ganglion cells to the magnocellular layers. We have developed a neurofibrillar stain which stains the M-ganglion cell population with a high degree of selectivity allowing us to map their distribution across the retina. As with other ganglion cell types the M-ganglion cell density peaks close to the fovea and declines towards the periphery. At 1 mm from the fovea the proportion of M-ganglion cells ranges from 6 to 10% and then increases to about 8-10% over much of the retina except along the nasal horizontal meridian. Along the nasal horizontal meridian the percentage increases from 10% at 7 mm eccentricity to 20% or more at higher eccentricities. The increased percentage of M-ganglion cells in the nasal quadrant of the retina correlates with the relatively smaller dendritic trees of M-ganglion cells in this region.

Animals↗

Cell density ratios in a foveal patch in macaque retina.

We examine the assumptions that the fovea contains equal numbers of inner (invaginating or ON) and outer (flat or OFF) midget bipolar cells and equal numbers of inner and outer diffuse bipolar cells. Based on reconstruction from electron photomicrographs of serial thin sections through the fovea of a macaque monkey, we reject both assumptions. First, every foveal L and M cone is presynaptic to one inner and one outer midget bipolar cell; however, S cones are presynaptic to one outer but no inner midget bipolar cell. Second, we measure the density of all foveal cells in the same patch of fovea, affording accurate cell density ratios. For each foveal cone pedicle, at a density of 26,500 mm(-2), there is close to one (0.88) outer diffuse bipolar cell but only 0.40 inner diffuse bipolar cells. This asymmetry may be related to differences in resolution and sensitivity for light increments and decrements. We also find one (1.01) Müller cell, one (1.01) amacrine cell in the inner nuclear layer, and close to one (0.83) horizontal cell for each cone pedicle. In addition, for each S cone, there are two inner S-cone bipolar cells and two small bistratified ganglion cells. In total, there are 3.4 cone bipolar cells per cone but only 2.6 ganglion cells per cone. The latter ratio is enough to accommodate one midget ganglion cell for each midget bipolar cell.

Animals↗

Enkephalin-like immunoreactivity in the cat superior colliculus: distribution, ultrastructure, and colocalization with GABA.

The distribution of enkephalin (ENK) immunoreactivity has been examined in the cat superior colliculus (SC) by means of light and electron microscope immunocytochemistry. The antisera were directed against leucine enkephalin but also recognized methionine enkephalin. Colocalization of ENK with gamma aminobutyric acid (GABA) was studied with a two-chromagen double-labeling technique. Enkephalin antiserum labeling was highly specific. Dense neuropil labeling was found only in a thin band 75-100 microns wide within the upper superficial gray layer of SC. Negligible neuropil labeling was seen deeper, except for patches of label within the intermediate gray layer. Intensely labeled neurons also had a specific distribution. Forty-seven percent were located within the upper 200 microns of SC, 40% within the deep superficial gray layer, 11% in the optic layer, and only 2% below that layer. Almost all ENK-labeled cells were small (mean area of 117 microns2). Some of these had horizontal fusiform cell bodies and horizontally oriented dendrites. Others had small round somata and thin, obliquely oriented dendrites. In double-labeling experiments, 18% of anti-ENK-labeled cells were also immunoreactive for GABA. Four distinct types of ENK-labeled profile were identified with the electron microscope. Presynaptic dendrites (PSD) with loose accumulations of synaptic vesicles were densely labeled with the antiserum. Conventional dendrites were also labeled. Both types of labeled profile received input from unlabeled synaptic terminals, including those from the retina that contained pale mitochondria and round synaptic vesicles and formed asymmetric synaptic contacts. Retinal terminals were never labeled with the antisera. However, some axon terminals with round synaptic vesicles, dark mitochondria, and symmetric synaptic densities were labeled by the antisera, as were some thinly myelinated axons. These results show that there is a small population of enkephalinergic neurons in the cat SC, some of which also contain GABA. Because not all cells with identical morphologies were double labeled, it appears that neurons of like morphology are chemically heterogeneous.

Animals↗

Calcium-binding proteins in the retina of a calbindin-null mutant mouse.

Calcium-binding proteins are abundantly expressed in many neurons of mammalian retinae. Their physiological roles are, however, largely unknown. This is particularly true for calcium-modulating proteins ("calcium buffers") such as calbindin D28k. Here, we have studied retinae of wildtype (+/+) and calbindin-null mutant (-/-) mice by using immunocytochemical methods. Although calbindin immunoreactivity was completely absent in the calbindin (-/-) retinae, those cells that express the protein in wildtype retinae, such as horizontal cells, were still present and appeared normal. This was verified by immunostaining horizontal cells for various neurofilament proteins. In order to assess whether other calcium-binding proteins are upregulated in the mutant mouse and may thus compensate for the loss of calbindin, mouse retinae were also immunolabeled for parvalbumin, calretinin, and a calmodulin-like protein (CALP). In no instance could a change in the expression pattern of these proteins be detected by immunocytochemical methods. Thus, our results show that calbindin is not required for the maintenance of the light-microscopic structure of the differentiated retina and suggest roles for this protein in retinal function.

Animals↗