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Results for “retinal plasticity”

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PubMed1989

Plasticity and differentiation of embryonic retinal cells after terminal mitosis.

The relation between terminal mitosis and the events that determine the developmental fate of embryonic precursor cells is not well understood. This relation has now been investigated with [3H]thymidine autoradiography to determine the time of cell birth and with a culture system that allows the testing of the developmental potential of cells isolated from the chick embryo retina. Contrary to the situation in vivo, where neuronal differentiation always precedes photoreceptor differentiation, photoreceptor differentiation occurs prematurely and precedes neuronal differentiation when precursor cells are isolated from the retina at early embryonic stages. Thus, cells born by embryonic day 5 (ED-5) give rise predominantly to photoreceptors when isolated for culture on ED-6 but develop mainly as neurons when isolated on ED-8. This suggests that retinal precursor cells retain after terminal mitosis the capacity to develop either as neurons or as photoreceptors. Moreover, photoreceptor differentiation appears to represent a constitutive or "default" pathway that precursor cells follow in the absence of neuron-inducing signals.

Animals↗
PubMed1994

Regulation of retinal ganglion cell axon arbor size by target availability: mechanisms of compression and expansion of the retinotectal projection.

The ability of pre- and postsynaptic populations to achieve the proper convergence ratios during development is especially critical in topographically mapped systems such as the retinotectal system. The ratio of retinal ganglion cells to their target cells in the optic tectum can be altered experimentally either by early partial tectal ablation, which results in an orderly compression of near-normal numbers of retinal projections into a smaller tectal area, or by early monocular enucleation, which results in the expansion of a reduced number of axons in a near-normal tectal volume. Our previous studies showed that changes in cell death and synaptic density consequent to these manipulations can account for only a minor component of this compensation for the population mismatch. In this study, we examine other mechanisms of population matching in the hamster retinotectal system. We used an in vitro horseradish peroxidase labeling method to trace individual retinal ganglion cell axons in superior colliculi partially ablated on the day of birth, as well as in colliculi contralateral to a monocular enucleation. We found that individual axon arbors within the partially lesioned tectum occupy a smaller area, with fewer branches and fewer terminal boutons, but preserve a normal bouton density. In contrast, ipsilaterally projecting axon arbors in monocularly enucleated animals occupy a greater area than in the normal condition, with a much larger arbor length and greater number of boutons and branches compared with normal ipsilaterally projecting cells. Alteration of axonal arborization of retinal ganglion cells is the main factor responsible for matching the retinal and tectal cell populations within the tectum. This process conserves normal electrophysiological function over a wide range of convergence ratios and may occur through strict selectivity of tectal cells for their normal number of inputs.

Animals↗
PubMed2003

Differential display implicates cyclophilin A in adult cortical plasticity.

Removal of retinal input from a restricted region of adult cat visual cortex leads to a substantial reorganization of the retinotopy within the sensory-deprived cortical zone. Little is known about the molecular mechanisms underlying this reorganization. We used differential mRNA display (DDRT-PCR) to compare gene expression patterns between normal control and reorganizing visual cortex (area 17-18), 3 days after induction of central retinal lesions. Systematic screening revealed a decrease in the mRNA encoding cyclophilin A in lesion-affected cortex. In situ hybridization and competitive PCR confirmed the decreased cyclophilin A mRNA levels in reorganizing cortex and extended this finding to longer postlesion survival times as well. Western blotting and immunocytochemistry extended these data to the protein level. In situ hybridization and immunocytochemistry further demonstrated that cyclophilin A mRNA and protein are present in neurons. To exclude the possibility that differences in neuronal activity per se can induce alterations in cyclophilin A mRNA and protein expression, we analyzed cyclophilin A expression in the dorsal lateral geniculate nucleus (dLGN) of retinally lesioned cats and in area 17 and the dLGN of isolated hemisphere cats. In these control experiments cyclophilin A mRNA and protein were distributed as in normal control subjects indicating that the decreased cyclophilin A levels, as observed in sensory-deprived area 17 of retinal lesion cats, are not merely a reflection of changes in neuronal activity. Instead our findings identify cyclophilin A, classically considered a housekeeping gene, as a gene with a brain plasticity-related expression in the central nervous system.

Amino Acid Sequence↗
PubMedDate not supplied

Monocular enucleation prevents retinal ganglion-cell loss following neonatal visual cortex damage in cats.

Damage to primary visual cortex (VC) in young cats leads to severe retrograde degeneration of the dorsal lateral geniculate nucleus (dLGN) and selective transneuronal retrograde degeneration of a class of retinal ganglion cells (RGCs) that have a medium-size soma. Previous studies have shown that "programmed" RGC death associated with normal development in one eye can be attenuated by removal of the other eye, suggesting that binocular interactions can influence developmental RGC death. The present study investigated whether removal of one eye also attenuates the ganglion cell loss that accompanies an early VC lesion. Five one-week-old cats received a unilateral VC lesion (areas 17, 18, and 19), and three of these cats also underwent monocular enucleation at the same time. Two normal control animals also were examined. RGC measurements were made from flat-mounted retinae when the animals were 5 weeks old. Sampling was restricted to a retinal area corresponding to the retinotopic representation included in the VC lesion. Results indicate that there is a marked loss of medium-size RGCs in the hemiretinae projecting to the damaged hemisphere in cats that received a VC lesion alone. However, there is no such loss in VC-lesion animals that also have a monocular enucleation. These results indicate that the transneuronal RGC loss that occurs after an early visual cortex lesion can be influenced by binocular interactions.

Aging↗
PubMed1989

Ribbon synapses of the mammalian retina contain two types of synaptic bodies--ribbons and spheres.

The present paper reports that the synaptic bodies of the retinal ribbon synapses in rat, guinea pig, golden hamster and mouse are a heterogeneous population of organelles. In addition to the well-known synaptic ribbons sensu stricto which consist of a platelike electron-dense central structure surrounded by electron-lucent synaptic vesicles, there are what is termed synaptic spheres, in which the core is not platelike, but round to oval. In rat retinae procured at day, ribbons outnumbered spheres by a factor of 4. At night spheres were not seen in photoreceptor cells. Spheres, like ribbons, may lie some distance from the synaptic site, perhaps indicating transit from their site of origin to the synapse. At night ribbons are longer than at daytime. In addition to the previously described connecting stalks between synaptic vesicles and the electron-dense ribbons, the presence of filamentous stalks between adjacent synaptic vesicles is described. The latter stalks, depending on their presence or absence, may influence the position of the synaptic vesicles in relation to the synaptic body and/or the presynaptic membrane. It is concluded that the plasticity of retinal synapses cannot be fully appreciated unless the temporal changes of ribbons, spheres and the connecting stalks are taken into consideration.

Animals↗
PubMedDate not supplied

Normal eye-specific patterning of retinal inputs to murine subcortical visual nuclei in the absence of brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is a preferred ligand for a member of the tropomyosin-related receptor family, trkB. Activation of trkB is implicated in various activity-independent as well as activity-dependent growth processes in many developing and mature neural systems. In the subcortical visual system, where electrical activity has been implicated in normal development, both differential survival, as well as remodeling of axonal arbors, have been suggested to contribute to eye-specific segregation of retinal ganglion cell inputs. Here, we tested whether BDNF is required for eye-specific segregation of visual inputs to the lateral geniculate nucleus and the superior colliculus, and two other major subcortical target fields in mice. We report that eye-specific patterning is normal in two mutants that lack BDNF expression during the segregation period: a germ-line knockout for BDNF, and a conditional mutant in which BDNF expression is absent or greatly reduced in the central nervous system. We conclude that the availability of BDNF is not necessary for eye-specific segregation in subcortical visual nuclei.

Animals↗
PubMed2006

Stabilization of axon branch dynamics by synaptic maturation.

The developmental refinement of topographic projections in the brain is reflected in the dynamic sculpting of axonal arbors that takes place as connections between CNS structures form and mature. To examine the role of synaptogenesis and synaptic maturation in the structural development of axonal projections during the formation of the topographic retinotectal projection, we coexpressed cytosolic fluorescent protein (FP) and FP-tagged synaptophysin (SYP) in small numbers of retinal ganglion cells in living albino Xenopus laevis tadpoles to reveal the distribution and dynamics of presynaptic sites within labeled retinotectal axons. Two-photon time-lapse observations followed by quantitative analysis of tagged SYP levels at individual synapses demonstrated the time course of synaptogenesis: increases in presynaptic punctum intensity are detectable within minutes of punctum emergence and continue over many hours. Puncta lifetimes correlate with their intensities. Furthermore, we found that axon arbor dynamics are affected by synaptic contacts. Axon branches retract past faintly labeled puncta but are locally stabilized at intensely labeled SYP puncta. Visual stimulation for 4 h enhanced the stability of the arbor at intense presynaptic puncta while concurrently inducing the retraction of exploratory branches with only faintly labeled or no synaptic sites.

Aging↗
PubMed1998

Neuroplasticity in the cat's visual system. Origin, termination, expansion, and increased coupling of the retino-geniculo-middle suprasylvian visual pathway following early ablations of areas 17 and 18.

We used anterograde and retrograde transsynaptic pathway tracing techniques to reveal the retinal origin and the cortical termination of the expanded retino-geniculo-middle suprasylvian (MS) cortex pathway in adult cats which sustained lesions of areas 17 and 18 on the day of birth (P1) or at 1 month of age (P28). Following anterograde transsynaptic transport of tritiated amino acids from the eye, four major results were obtained: (1) a strong and specific pathway from retina through dorsal lateral geniculate nucleus (dLGN) to the posterior half of MS cortex was identified; this pathway is a substantial expansion of an insignificant pathway present in intact cats; (2) the terminus of the pathway was lower layer III and layer IV; (3) contralateral projections were stronger than ipsilateral projections; (4) projections in P28 cats were stronger than those in P1 cats. Following retrograde transsynaptic transport of WGA-HRP from posterior MS cortex, four additional results were obtained: (1) the pathway was enlarged and visuotopically organized; (2) the pathway arose primarily from alpha- and gamma-retinal ganglion cells; (3) a small number of beta-cells in P1 cats and a modest number in P28 cats also contribute to the pathway; (4) the combined numbers of gamma- and beta-cells relative to alpha-cells was greater in temporal retina than in nasal retina. The combined demonstration of both origin and terminus of the pathway with transsynaptic tracers argued strongly for high levels of coupling between primary and secondary pathway limbs in both P1 and P28 cats. This level of coupling, as well as other features of the pathway, have much in common with the retino-geniculo-17/18 pathway of intact cats. However, the retino-geniculo-MS system in P1 cats transmits primarily Y and W signals, in P28 cats X, Y, and W signals; whereas the retino-geniculo-17/18 pathway transmits primarily X and Y signals. These results have implications for understanding the repercussions of early visual cortex lesions in monkeys and humans.

Amino Acids↗
PubMed1985

Vascular casting and scanning electron microscopy of human ocular vascular abnormalities.

Plastic casts of ocular vessels were made from postmortem specimens obtained from patients who had had hypertension and arteriosclerosis, diabetes mellitus, and retinopathy of childhood. In conjunction with scanning electron microscopy, the casts serve as models of pathologic vascular changes, including arteriovenous crossing defects, microaneurysm, localized capillary nonperfusion, and rapidly growing peripheral choroidal vessels. These preliminary findings should serve to encourage further study of ocular vascular abnormalities with the use of plastic casting techniques.

Adult↗
PubMed2002

Tuning of photoreceptor function in three mantis shrimp species that inhabit a range of depths. II. Filter pigments.

Within single species of stomatopod crustaceans, visual pigment classes of homologous photoreceptors throughout the retina are identical in all individuals and do not vary with the spectral characteristics of local habitats. We examined whether spectral sensitivities of stomatopod photoreceptors are differentially tuned through variations in the filter pigments associated with particular receptor classes. All classes of intrarhabdomal filters were characterized using microspectrophotometry in retinas of three stomatopod species, Haptosquilla trispinosa, Gonodactylellus affinis, and Gonodactylopsis spongicola, comparing individuals of each species collected from shallow or deep water. Depending on the depth of collection, filters varied among individuals both in optical density and in spectral shape, and the variation that was observed was similar in all three species. The changes in filter density and spectrum increased absolute sensitivity in retinas of animals living at greater depths, and tuned their long-wavelength photoreceptors for improved function in the bluer light available in deep water. Plasticity in retinal spectral function may be common in mantis shrimp species that occupy a range of habitat depths.

Animals↗
PubMed2026

Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.

Retinal organoids represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but the capacity of host cone bipolar cells in the primate macula to rewire with transplanted photoreceptors has not been established. In this study, we transplanted genome-edited ISL1-/- human retinal organoids lacking ON-bipolar cells into an acute laser-induced macular photoreceptor ablation non-human primate model. Using immunohistochemistry, ultrastructural imaging, and focal macular electroretinography, we demonstrate that host rod and cone bipolar cells actively extend dendrites toward grafted photoreceptors and form synaptic contacts, with evidence of functional signal transmission in a subset of transplanted eyes. Longitudinal, per-eye analyses revealed that host ON-bipolar responses improved in two of four eyes with ISL1-/- graft by up to 21.6% and remained stable for up to 2 years post transplantation. Moreover, OFF-pathway connectivity showed potential progressive maturation, with delayed increase in d-wave after 13 months in one of those eyes. These findings provide the first demonstration of long-term anatomical host-graft synaptic integration in the primate macula, establishing that central cone bipolar circuits retain the capacity for durable rewiring with human stem-cell-derived grafts. Our results highlight ISL1-/- retinal organoids as a promising approach for central vision restoration in macular degeneration.

Animals↗
PubMed1996

Synaptic activity and the construction of cortical circuits.

Vision is critical for the functional and structural maturation of connections in the mammalian visual system. Visual experience, however, is a subset of a more general requirement for neural activity in transforming immature circuits into the organized connections that subserve adult brain function. Early in development, internally generated spontaneous activity sculpts circuits on the basis of the brain's "best guess" at the initial configuration of connections necessary for function and survival. With maturation of the sense organs, the developing brain relies less on spontaneous activity and increasingly on sensory experience. The sequential combination of spontaneously generated and experience-dependent neural activity endows the brain with an ongoing ability to accommodate to dynamically changing inputs during development and throughout life.

Action Potentials↗
PubMed2006

Cyclops.

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Amblyopia↗
PubMed1981

Visual-vestibular interaction in multiple sclerosis.

Visual modulation of the vestibuloocular reflex (VOR) was analyzed in 20 patients with multiple sclerosis who had no vestibular or ocular motor symptoms. Visual suppression of the VOR was impaired in 75% of patients. VOR gains in darkness were elevated in 35% of patients. Elevated VOR gain in darkness is attributed to vestibular adaptation to defective smooth pursuit. This vestibular plasticity achieved retinal image stability by matching eye velocity to head velocity when stationary targets were viewed. The high incidence of impaired visual suppression of the VOR rivals the sensitivity of other physiologic tests used to identify multiple sclerosis.

Adult↗
PubMed2006

Synaptic plasticity in CNGA3(-/-) mice: cone bipolar cells react on the missing cone input and form ectopic synapses with rods.

In the mammalian retina, rods and cones connect to distinct sets of bipolar cells. Rods are presynaptic to a single type of rod bipolar cell, whereas cones connect to different types of cone bipolar cells. Synaptic rewiring between cone photoreceptor terminals and rod bipolar cell dendrites has been described as a general result of photoreceptor degeneration. To investigate whether cone bipolar cells also show synaptic plasticity in the absence of cone input, we studied the connectivity of cone bipolar cell dendrites in CNGA3(-/-) mice, a model with specific loss of cone photoreceptor function. Dendritic connections of ON and OFF cone bipolar cells were visualized using specific cell markers or by intracellular injection with fluorescent dyes. The results show that cone bipolar cells in CNGA3(-/-) mice form ectopic synapses with rods. In contrast, cone bipolar cells do not form ectopic synapses with rods in CNGA3(-/-)Rho(-/-) mice, in which both types of photoreceptors are nonfunctional. In analogy with these results, we found that input-deprived rod bipolar cells form ectopic synapses with functional cones in Rho(-/-) mice but not with inoperable cones in the CNGA3(-/-)Rho(-/-) mouse. Our data indicate that the formation of ectopic bipolar cell synapses in the outer plexiform layer requires a functional presynaptic photoreceptor.

Animals↗