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PubMedDate not supplied

[Differentiation of the retina and pigment epithelium in the ontogeny of the common frog. 1. The retina].

Changes in the ultrastructure of the differentiating retinal cells were studied by means of electron microscopy in Rana temporaria at successive developmental stages. Common features of the onset of differentiation of the retinal cells have been shown: appearance of the granular endoplasmic reticulum elements, of the polysomes, beginning of utilization of the yolk and lipids, elimination of ovarial melanosomes. Later during the differentiation of retinal neurons the protein synthesizing machinery and Golgi complex of these cells develop markedly, the number of mitochondria increases. The differentiation of retina begins from the Müllerian cells (stage 28) which determine the direction of growth of the neuron processes. They are followed by the ganglion cells and photoreceptors (stage 29). The signs of differentiation of the inner nuclear layer neurons become apparent later, in the amacrine and horizontal cells at the same time and in the bipolars later. The main features of neuronal organization of the retina which determine the structural basis of its function of light perception are formed by stage 40.

Animals↗

PubMed1977

Retinal structure in Synbranchus marmoratus with observations on two new cone myoid inclusions.

The retina of a South American swamp eel, Synbranchus marmoratus (Synbranchidae), was studied by Golgi impregnation, light and electron microscopy. Its principal features include (1) the presence of a dense matrix, possibly a new type of tapetum lucidum, in the pigment epithelium, (2) a well developed photoreceptor layer containing large rods, single, double and triple cones, and (3) well developped inner nuclear and plexiform layers, with the exception of horizontal cells which are few and relatively small. These and other observations are discussed in relation to the photic environment and habits of this fish. The presence of microfilament bundles and two unusual features, microtubuleladen dense bodies and paracrystalline inclusions, in cone myoids are discussed in terms of their possible involvement in retinomotor responses.

Animals↗

PubMedDate not supplied

Origins of the electroretinogram oscillatory potentials in the rabbit retina.

The electroretinogram (ERG) oscillatory potential (OP) is a high-frequency, low-amplitude potential that is superimposed on the rising phase of the b-wave. It provides noninvasive evaluation of inner retina function in vivo and is a useful tool in basic research as well as in the clinic. While the OP is widely believed to be generated mainly by activity of the inner retina, the exact underlying neural mechanisms are not well understood. We have investigated the retinal mechanisms that underlie OP generation in Dutch-belted rabbits. The OP was isolated by band-filtering (100-1000 Hz) ERG signals. We used pharmacological agents that block specific transmitter receptors or voltage-gated channels in order to examine contributions of various retinal mechanisms to OP generation. Our results show that the OP elicited by a bright brief flash can be classified into early, intermediate, and late subgroups that are likely generated mainly by photoreceptors, action-potential-independent, and action-potential-dependent mechanisms in the ON pathway of the inner retina, respectively. ON bipolar cells themselves make only a small direct contribution to OP generation, as do horizontal cells and neurons in the OFF pathway.

Action Potentials↗

PubMed1994

Nitric oxide induces light-adaptive morphological changes in retinal neurones.

This study tested the possible involvement of nitric oxide (NO) in light-adaptive morphological changes in the outer retina of a cyprinid fish, the roach. Isolated retinae were treated in the dark by either of two NO-donor compounds (S-nitroso-n-acetylpenicillamine and sodium nitroprusside) and then studied by light and electron microscopy; similar results were obtained in both cases. Application of NO induced contraction of cone photo-receptor myoids (i.e. retinomotor movements) and formation of horizontal cell spinules. Accordingly the cone index and the spinule/ribbon ratio showed 15-20% and 49-95% change, respectively, compared with controls. These results are consistent with involvement of NO in the light adaptation process in the outer retina of teleost fish.

Adaptation, Physiological↗

PubMed1984

Effects of accessory optic system lesions on vestibulo-ocular and optokinetic reflexes in the cat.

Horizontal vestibulo-ocular reflex (VOR) and optokinetic nystagmus (OKN) were studied before and after lesions within the accessory optic system (AOS) in the cat. Post-lesion retinal input to the AOS was evaluated using the autoradiographic technique. Unilateral lesion of the lateral terminal nucleus of the AOS (LTN) and the resulting retinal deafferentation of the medial terminal nucleus of the AOS (MTN) induced a spontaneous nystagmus in the dark whose slow phase was directed ipsilaterally to the lesion. VOR gain was reduced for both directions with a maximal decrease for stimulation directed ipsilaterally to the lesion. OKN gain obtained for both directions of binocular stimulation was decreased, mainly when the stimulus was directed contralaterally to the lesion. After two post-operative weeks, spontaneous nystagmus disappeared and the VOR symmetry recovered simultaneously. A symmetrical OKN was only observed after one month. In spite of the known visual selectivity for vertical direction in LTN-MTN cells, the results of this study support a functional involvement of these nuclei in horizontal VOR and OKN.

Animals↗

PubMed1997

The horizontal optokinetic reflex of the opossum (Didelphis marsupialis aurita): physiological and anatomical studies in normal and early monoenucleated specimens.

In the opossum the symmetrical binocular horizontal optokinetic nystagmus gives way to an asymmetrical monocular reflex: the nasotemporal (NT) stimulation yielding lower gain than the temporonasal (TN). In adults, monocularly enucleated at postnatal days 21-25 (pnd21-25), the gain of NT responses is markedly increased, approaching that of TN. Severe cell loss was detected in the nucleus of the optic tract (NOT) on the deafferented side in early monoenucleated specimens. In normal animals retinal afferents to the NOT are all crossed, while in animals enucleated at pnd21-25 sparse uncrossed retinal elements were observed. Although this abnormal projection might influence the increased NT response in this subgroup, it is argued that the increased symmetry in monoenucleated opossums may be the result of changes mediated by the commissural connection between both NOTs.

Animals↗

PubMed1986

Experimental chloroquine retinopathy.

Chloroquine retinopathy was produced experimentally in the eye of the albino corydoras (one of the tropical fish) by daily administration of chloroquine (0.1 mg per os). The enucleated eyes were examined from the 14th day to 3 months after the beginning of drug administration under light and electron microscopy. The first change of retina was the appearance of membraneous cytoplasmic body (MCB) in the cytoplasm of ganglion, amacrine, bipolar and horizontal cells. MCB might be degenerated lysosome. They showed lamellar figures or crystalline lattice-like structures. Secondarily, these MCB appeared in the inner segments of photoreceptor cells. The outer segments of rod cells disappeared, and then those of cone cells. Although photoreceptor cells were diminished in number in advanced degeneration, the cells of inner nuclear layer and ganglion cells were maintained in number. The presence of MCB dose not mean death of cells. The retinal pigment epithelial cells contained MCB in its cytoplasm only in severe degenerative cases, and did not show other remarkable changes. MCB also appeared in the cytoplasm of pericytes of retinal vessels. Chloroquine is considered to damage directly photoreceptor cells most severely.

Animals↗

PubMed2000

Taurine blocks spontaneous cone contraction but not horizontal cell dark suppression in isolated goldfish retina.

The objective of this study was to investigate the effects of taurine on cone retinomotor movements and the responses of cone-driven horizontal cells in dark-adapted teleost retina. In isolated goldfish retina preparations maintained in the dark, cones spontaneously contracted, and the responses of horizontal cells were suppressed. Addition of 5 mM taurine to the physiological solution blocked the spontaneous contraction of cones in the dark but did not block the dark-suppression of horizontal cell responses. These results indicate that the mechanism that leads to horizontal cell dark suppression is not sensitive to taurine. Although both cone retinomotor position and horizontal cell responsiveness are known to be modulated by dopamine, the present results do not support the hypothesis that taurine inhibits dopamine release in the dark because only spontaneous cone contraction was affected by taurine. These results also indicate that spontaneous cone contraction in the dark is not the cause of horizontal cell dark suppression because, in the presence of taurine, cones were elongated yet horizontal cell responses were still suppressed. Consequently, these results make it clear that horizontal cell dark suppression is not an artifact produced by incubating isolated teleost retina preparations in taurine-free physiological solution.

Adaptation, Ocular↗

PubMed1988

Catecholaminergic subpopulation of retinal displaced ganglion cells projects to the accessory optic nucleus in the pigeon (Columba livia).

In birds, displaced ganglion cells (DGCs) constitute the exclusive source of retinal input to the nucleus of the basal optic root (nBOR) of the accessory optic system. Tyrosine-hydroxylase (TH) immunoreactivity was examined in the pigeon retina after injections of rhodamine-labeled microspheres into the nBOR. A population of about 400 DGCs was observed in each case to exhibit both TH immunoreactivity and rhodamine bead fluorescence. This corresponded to about 10-15% of the total number of identified DGCs in each retina. Double-labeled cells were medium- to large-size (12 to 20 microns in the largest axis) and were always located at the border between the inner nuclear and the inner plexiform layers. Their dendrites could be followed horizontally in lamina 1 of the inner plexiform layer for up to 300 microns from the cell body. The distribution of double-labeled DGCs appeared to be mostly peripheral, matching the overall distribution of identified DGCs. Larger DGCs (21-28 microns) were never seen to contain TH immunoreactivity. Examination of brain sections revealed plexuses of thin varicose TH-positive axons in all subdivisions of the nBOR. Unilateral enucleation produced an almost complete elimination of TH immunoreactivity in the contralateral nucleus. Such results suggest the existence of a population of catecholaminergic DGCs projecting into the accessory optic system of the pigeon. They also support the emerging hypothesis concerning the neurotransmitter heterogeneity of ganglion cells in the vertebrate retina.

Animals↗

PubMed2003

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina.

AIMS/HYPOTHESIS: Neurodegenerative changes in the diabetic retina occurring before diabetic retinopathy could be inevitable by the altered energy (glucose) metabolism, in the sense that dynamic image-processing activity of the retinal neurons is exclusively dependent on glucose. We therefore investigated the morphological changes in the neural retina, including neuronal cell death, of a streptozotocin-induced model of diabetes. METHODS: Streptozotocin was intravenously injected. Rats were maintained hyperglycaemic without insulin treatment for 1 week and 4, 8, 12, and 24 weeks, respectively. Diabetic retinas were processed for histology, electron microscopy, and immunohistochemistry using the TUNEL method. RESULTS: A slight reduction in the thickness of the inner retina was observed throughout the diabetic retinas and a remarkable reduction was seen in the outer nuclear layer 24 weeks after the onset of diabetes. The post-synaptic processes of horizontal cells in the deep invaginations of the photoreceptors showed degeneration changes from 1 week onwards. A few necrotic ganglion cells were observed after 4 weeks. At 12 weeks, some amacrine cells and a few horizontal cells showed necrotic features. Three to seven cellular layers in the outer nuclear layer and nerve terminals, rolled by the fine processes of the Müller cells near the somata of the degenerated ganglion cells, were apparent at 24 weeks. Apoptosis appeared in a few photoreceptor cells at 4 weeks, and the number of apoptotic photoreceptors increased thereafter. CONCLUSION/INTERPRETATION: These findings suggest that the visual loss associated with diabetic retinopathy could be attributed to an early phase of substantial photoreceptor loss, in addition to later microangiopathy.

Animals↗

PubMed1996

Expression of neurotrophins and trk receptors in the avian retina.

Using the RNase protection assay, we have found that nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are expressed in the avian retina during development. The expression peaks around embryonic days 12-15, with decreasing levels at later stages of development. Abundant levels of NGF and BDNF but low levels of NT-3 mRNA were found in the adult retina. We also found that light/darkness regulated the levels of NGF and BDNF mRNAs but not the levels of NT-3 mRNA in the 5-day-old chicken retina. It was demonstrated that NGF and BDNF mRNA levels were up-regulated by light exposure. The cellular localization of mRNA expression for the neurotrophins and neurotrophin receptors TrkA, TrkB, and TrkC in the retina was studied using in situ hybridization. The patterns of NGF and trkA mRNA expression were very similar and were localized to the external part of the inner nuclear layer on the border with the outer plexiform layer and corresponded to the localization of horizontal cells. NT-3 labeling was also found over the external part of the inner nuclear layer, whereas trkC mRNA was found over all layers in the retina. BDNF labeling was found over all layers in the retina, whereas TrkB labeling was intense over cells in the ganglion cell layer, which is in agreement with the response of ganglion cells to BDNF stimulation. Functional neurotrophin receptors were suggested by the response of retinal explants to neurotrophin stimulation. These data indicate that the neurotrophins play local roles in the retina that involve interactions between specific neuronal populations, which were identified by the localization of the Trk receptor expression. The data also suggest that NGF and BDNF expression is regulated by normal neuron usage in the retina.

Animals↗

PubMed2001

Muscarinic acetylcholine receptors in the normal, developing and regenerating newt retinas.

Immunoreactivity for m2 and m4 muscarinic acetylcholine receptors (mAChRs) was demonstrated in the adult newt retina. The m2 mAChR was localized to somata on either side of the inner plexiform layer (IPL), especially ganglion cells, and also distributed into two bands within the IPL. The distal band at a depth of 0-15% IPL co-localized with one of two choline acetyltransferase (ChAT) immunoreactive bands, while the proximal band at 85-100% depth did not overlap with either of the ChAT-ir bands. The m4 mAChR was localized to somata closely apposed to either side of the IPL, probably amacrine cell somata, and no immunoreactivity was detectable throughout the IPL. The time course of appearance of the m2 and m4 mAChRs was examined in both developing and regenerating retinas. Like acetylcholinesterase (AChE), the m2 was first detected in somata located at the most proximal level of the retina well before ChAT-ir cholinergic neurons appeared, while the m4 was detected at the time of appearance of ChAT, in both developing and regenerating retinas. When the outer plexiform layer (OPL) began to form, somata in the horizontal cell layer became transiently immunoreactive to the m2. The discrepancy in distribution of the m2 and ChAT in the IPL suggests that mAChR may play a role other than cholinergic neurotransmission. Furthermore, the similarity in time course of appearance of the m2 and m4, as well as other cholinergic system components [4], in both developing and regenerating retinas would suggest that the mechanisms that control neuronal differentiation during retinal development and regeneration are similar.

Acetylcholinesterase↗

PubMed1994

Target recognition and visual maps in the thalamus of achiasmatic dogs.

Vision is dependent on ordered neuronal representations or maps of visual space. These maps depend on precise connections between retinal axons and their targets cells. In mammals, nerve fibres from right and left eyes produce congruent maps of contralateral visual space in adjacent layers of the lateral geniculate nucleus (LGN). We have identified an autosomal recessive mutation in Belgian sheepdogs that eliminates the optic chiasm. In these mutants, all retinal axons project into the ipsilateral optic tract, including those originating in the nasal hemiretina that normally cross midline. These animals exhibit a pronounced horizontal nystagmus. The abnormal ipsilaterally directed nasal fibres innervate the LGN as if they had successfully crossed the midline, terminating in the appropriate layer of the nucleus. As a consequence, the LGN contains non-congruent, mirror-image maps of visual space in adjacent layers. These results show that there is a robust affinity between nasal and temporal retinal axons and specific LGN layers even when all retinal axons originate from a single eye.

Animals↗

PubMed1996

Histology of fetal eyes with oculocutaneous albinism.

The diagnosis of tyrosinase-negative oculocutaneous albinism (OCA) was made in a 19-week-old fetus by skin biopsy. Because the parents had an 11-year-old son with tyrosinase-negative OCA, they requested that the fetus be aborted at the 20th week of gestation. A histological analysis of the eyes was performed. Throughout the retina, the ganglion cell layer was separated from the inner neuroblastic layer by the inner plexiform layer. However, the number of ganglion cells was decreased and the nerve fiber layer was immature. Bipolar and horizontal cells had begun to segregate into the inner nuclear layer. Rods and cones were identifiable in the posterior, but not peripheral, retina. Cones were more numerous in the center of the retina, and no rod-free area was identifiable. In addition, the ciliary body (epithelial folds, blood vessels in the mesodermal connective tissue core, and ciliary muscle) was less developed than in a normal fetus. Melanosomes in the retinal pigment epithelium only contained filaments without melanization and were therefore classified as stage I or II melanosomes. However, the ciliary epithelium also contained some stage III melanosomes with melanin adherent to the filaments.

Abortion, Therapeutic↗

PubMed1990

Correlation between retinal afferent distribution, neuronal size, and functional activity in the guinea pig medial terminal accessory optic nucleus.

The intrinsic morpho-functional organization of the medial terminal nucleus of the accessory optic system was investigated in the guinea pig. The distribution of the retinal afferents, as assessed by the axoplasmic transport of 14C-valine, showed a remarkable asymmetry within the nucleus. Thus, while the retinal terminal field covered the entire medial terminal nucleus, by far the largest density of labeled retinofugal axon terminals was found within its dorsal division. In this same portion of the nucleus, we found the greatest density of large cells and the maximum intensity of functional activation, this latter as estimated by the increase in metabolic activity of neurons using the 14C-2-deoxyglucose autoradiographic method in the vertical and horizontal whole-field movement in the visual field.

Amino Acids↗

PubMed1989

Collection and handling of ultrathin serial sections for 3-dimensional reconstruction.

Serial sectioning for 3-D reconstruction requires a highly skilled and experienced individual to collect ribbons of ultrathin sections on formvar-coated grids, and to handle the grids after section collection. A simple method is described for placing ribbons in an orderly serial fashion on formvar-coated grids, by a microtomist with average experience. Prior to sectioning, a wax ledge is prepared on the sloping edge of a glass knife in order to support a formvar-coated grid held in a horizontal slot cut in the wax. After a ribbon is formed, the water in the trough is slowly withdrawn to allow the ribbon to settle on the grid. The grids are then placed in an easy-to-make plastic chamber so that the formvar does not get ruptured during drying. The chamber can also be used for staining and storage of grids thereafter. Approximately 4000 sections from mudpuppy retinal cells have been successfully collected using this method. Computer 3-D reconstruction of the individual cells has been done.

Microscopy, Electron↗

PubMedDate not supplied

Signal clipping by the rod output synapse.

The properties of synapses between retinal neurons make an essential contribution to early visual processing. Light produces a graded hyperpolarization in photoreceptors, up to 25 mV in amplitude, and it is conventionally assumed that all of this response range is available for coding visual information. We report here, however, that the rod output synapse rectifies strongly, so that only potential changes within 5 mV of the rod dark potential are transmitted effectively to postsynaptic horizontal cells. This finding is consistent with the voltage-dependence of the calcium current presumed to control neurotransmitter release from rods. It suggests functional roles for the strong electrical coupling of adjacent rods and the weak electrical coupling of adjacent rods and cones. The existence of photoreceptor coupling resolves the apparent paradox that rods have a 25 mV response range, while signals greater than 5 mV in amplitude are clipped during synaptic transmission. We predict that the strengths of rod-rod and rod-cone coupling are quantitatively linked to the relationship between the rod response range and the synapse operating range.

Animals↗

PubMed1991

Release of endogenous excitatory amino acids from ON-type bipolar cells isolated from the goldfish retina.

Excitatory amino acids are presumed to be the transmitter of retinal bipolar cells. However, one of the essential criteria for the identification of the transmitter, its release from the cells upon depolarization, has not been demonstrated. This article examines the release of endogenous excitatory amino acids from bipolar cells and correlates this release with the influx of Ca2+. Bipolar cells with a large, bulblike axon terminal (ON-type cells with mixed inputs from rods and cones) were enzymatically isolated from the goldfish retina. Horizontal cells dissociated from the catfish retina were used as a probe of excitatory amino acids, because these cells can detect submicromolar concentrations of L-glutamate with high selectivity. An isolated bipolar cell was closely apposed to a dissociated horizontal cell, and each cell was voltage clamped by a patch pipette in the whole-cell clamp configuration. When the bipolar cell was depolarized from -60 mV to a potential more positive than -40 mV using a 500-msec voltage pulse, an outward current (greater than 20 pA) was recorded from the apposed horizontal cell, which was maintained at +40 mV. The reversal potential of the current induced by the substance released from bipolar cells (Irs) was close to 0 mV and was almost identical to the responses evoked with ionophoretically applied L-glutamate. Both reversal potentials were shifted to the same, more negative value when the external Na+ was replaced with choline. Furthermore, the Irs was suppressed reversibly by the application of kynurenic acid, a glutamate antagonist. When the Ca current (ICa) of the bipolar cell was blocked by Cd2+, the Irs also disappeared. The peak amplitude of Irs was closely related to that of the ICa. We conclude that mixed rod/cone ON-type bipolar cells of the goldfish retina release an endogenous excitatory amino acid or a closely related compound in a Ca(2+)-dependent manner.

Amino Acids↗