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PubMed1989

Extrinsic determinants of retinal ganglion cell development in primates.

As in all mammals studied to date, primate retina contains morphologically distinct classes of retinal ganglion cells (Polyak: The Retina. Chicago: University of Chicago Press, '41; Boycott and Dowling: Philos. Trans. R. Soc. Lond. [Biol.] 225:109-184, '69; Leventhal et al.: Science 213:1139-1142, '81; Perry et al.: Neuroscience 12:1101-1123, '84; Rodieck et al.: J. Comp. Neurol. 233:115-132, '85; Rodieck: In H.D. Steklis and J. Erwin (eds): Comparative Primate Biology, Volume 4: Neurosciences. New York: Alan R. Liss, Inc., pp. 203-278, '88). We have now studied the morphologies, central projections, and retinal distributions of the major morphological classes of ganglion cells in the normal adult monkey, the newborn monkey, and the adult monkey in which restricted regions of retina were depleted of ganglion cells at birth as a result of small lesions made around the perimeter of the optic disc. Both old-world (Macaca fascicularis) and new-world (Saimiri sciureus) monkeys were studied. Our results indicate that, at birth, the major morphological classes of monkey retinal ganglion cells are recognizable; cells in central regions are close to adult size whereas cells in peripheral regions are much smaller than in the adult. As in the adult (Stone et al.: J. Comp. Neurol. 150:333-348, '73), in newborn monkeys there is a very sharp division between ipsilaterally and contralaterally projecting retinal ganglion cells (nasotemporal division). Consistent with earlier work (Hendrickson and Kupfer: Invest. Ophthalmol. 15:746-756, '76) we find that the foveal pit in the neonate is immature and contains many more ganglion cells than in the adult. In the adult monkey in which the density of retinal ganglion cells in the central retina was reduced experimentally at birth, the fovea appeared immature, and an abnormally large number of retinal ganglion cells were distributed throughout the foveal pit. The cell bodies and dendritic fields of ganglion cells that developed within cell-poor regions of the central retina were nearly ten times larger than normal. In peripheral regions the effects were smaller. The dendrites of the abnormally toward the foveal pit. They did not extend preferentially into the cell-poor region as do the abnormally large cells on the borders of experimentally induced cell-poor regions of cat central retina (Leventhal et al.: J. Neurosci. 8:1485-1499, '88) or, as we found here, in paracentral regions of primate retina.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1987

Perinatal retinal haemorrhages and development. Follow-up in seven year olds.

Depending on methods of delivery, 7-50% of all children are born with retinal haemorrhages (RH). To assess the prognostic value of extensive RH for the future development of the child, the ophthalmological, neurological and psychological status of 52 children, 26 born with RH and 26 controls, were examined at the age of seven years. There were significant differences between the two groups using only psychological measures. Children with RH performed poorer than the control group, but the results did not point to any particular cerebral areas being affected. However, children with both RH and low socio-economic status were significantly less emotionally stable than the controls. Socio-economic factors also seem to be more highly correlated with later performance than do RH.

Child↗
PubMed1981

Chorioretinal dysplasia in young subjects with Wagner's hereditary vitreoretinal degeneration.

Six young patients from three pedigrees with Wagner's disease were submitted to fluorescein angiography of the peripheral fundus. All eyes showed aberrant areas, characterized by: 1. localization principally in equatorial region of temporal half of the fundus. 2. whitish appearance of neuroretina with sharp demarcations. 3. absence of retinal vasculature. 4. marked atrophy of choriocapillaris and retinal pigment epithelium. 5. abnormal deflections of retinal vessels at the posterior margin of these areas. Arguments are presented in support of the hypothesis that these areas were dysplastic and not degenerative. The difference with lattice degeneration, another wellknown finding in Wagner's disease, is that retinal vasculature never developed in the dysplastic peripheral areas. It is probable that hypoplasia of the choroid has led to a too inferior structure of the overlying retina to permit development of retinal vessels. The frequent occurrence of retinal breaks in young patients with Wagner's disease, especially in the temporal periphery, seems to be a consequence of the poor condition of the retina in these dysplastic areas caused by the inferior development of both retinal and choroidal vasculature.

Adolescent↗
PubMed1998

Spontaneous resolution of retinal detachment occurring after macular hole surgery.

OBJECTIVE: To document the spontaneous resolution of retinal detachment developing after macular hole surgery. METHODS: We identified all patients who developed a postoperative retinal detachment after undergoing macular hole surgery at Washington University School of Medicine, St Louis, Mo; the surgery was performed by one of us (L.V.D.P. or H.J.K.) between 1991 and 1996. RESULTS: Six of 73 eyes developed a postoperative retinal detachment; the retinal detachment was inferior in all cases. Two eyes that had inferior retinal breaks underwent further surgery to repair the retinal detachment. Retinal breaks could not be identified in the other 4 eyes; the retinal detachment resolved without further surgery in all 4 of these eyes. CONCLUSION: The recognition that retinal detachment occurring after macular hole surgery can resolve without additional surgery may result in the avoidance of further surgical intervention in some eyes.

Aged↗
PubMed1979

Selection of appropriate medial branch of the optic tract by fibres of ventral retinal origin during development and in regeneration: an autoradiographic study in Xenopus.

The formation of the branches of the optic tract has been studied with the use of [3H]proline autoradiography, during development and during regeneration of the optic nerve in Xenopus with one compound ventral (VV) eye made by the embryonic fusion of two ventral eye fragments. The formation of the optic pathway was abnormal in that the lateral branch failed to develop, suggesting that fibres from a VV retina selectively entered the tectum via the medial branch during development. Three months after section of the optic nerve of a VV eye, regenerated fibres were present both in the contralateral and ipsilateral tecta. On the ipsilateral side regenerated fibres entered the tectum via the medial branch only. Retinal fibres entered the contralateral tectum through both branches in some animals and through the medial branch only in others. It is concluded that mechanical factors alone are insufficient to explain the phenomenon of selection of the appropriate medial branch by fibres of ventral retinal origin either during development or in regeneration. Some form of fibre-substrate interaction seems to be necessary; and this ability of fibres from a VV eye to take the path appropriate for ventral retina argues strongly that the VV eye is not a regulated system in terms of cell specificities.

Animals↗
PubMed2005

The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development.

In the mouse retina, at least ten distinct types of bipolar interneurons are involved in the transmission of visual signals from photoreceptors to ganglion cells. How bipolar interneuron diversity is generated during retinal development is poorly understood. Here, we show that Irx5, a member of the Iroquois homeobox gene family, is expressed in developing bipolar cells starting at postnatal day 5 and is localized to a subset of cone bipolar cells in the mature mouse retina. In Irx5-deficient mice, defects were observed in the expression of some, but not all, immunohistological markers that define mature Type 2 and Type 3 OFF cone bipolar cells, indicating a role for Irx5 in bipolar cell differentiation. The differentiation of these two bipolar cell types has previously been shown to require the homeodomain-CVC transcription factor, Vsx1. However, the defects observed in Irx5-deficient retinas do not coincide with a reduction of Vsx1 expression, and conversely, the expression of Irx5 in cone bipolar cells does not require the presence of a functional Vsx1 allele. These results indicate that there are at least two distinct genetic pathways (Irx5-dependent and Vsx1-dependent) regulating the development of Type 2 and Type 3 cone bipolar cells.

Animals↗
PubMed1992

Oxygen-induced retinopathy in the rat: hemorrhages and dysplasias may lead to retinal detachment.

Rearing neonatal rats in hyperoxia induces the development of retinal hemorrhages and retinal dysplasia. Albino rats were placed in 80% oxygen immediately after birth and were exposed for either 5, 10, or 14 days, followed by sacrifice or exposure to normoxia for an additional 2, 4, 5, 7, 8, 10, 38, 45 or 56 days. Control rats were simultaneously raised in room air and sacrificed at the same times. All animals were enucleated and their eyes processed for light and electron microscopy. Eyecups were trimmed to facilitate cross-sectioning of the retina in the vertical meridian. No control rats showed signs of retinal hemorrhages or of dysplastic folds or rosettes. Nor did the retinas of rats killed immediately after oxygen exposure contain hemorrhages, but the incidence of retinal folds or rosettes in this group was 54%. For rats exposed to combinations of hyperoxia and brief normoxia (10 days or less), 40% suffered hemorrhages and 50% developed retinal folds or rosettes. Although hemorrhages were more prominent in rats subjected to longer periods of oxygen (73% of all rats exposed for 14 days followed by brief normoxia vs. 6% of those exposed for 5 days followed by brief normoxia), the incidence decreased with time post-exposure in room air. Hemorrhages occurred in 100% of the rats raised in oxygen for 14 days followed by 2 days in room air, and decreased to 50% by 7 days in room air and to 0% by 38 days, indicating a spontaneous resolution with time. In each case, the blood appeared to leak from the newly-forming vessels of the deep capillary net, with most of the red blood cells migrating to the subretinal space. Retinal fold or rosette formation, indicative of developmental dysplasia, occurred in a fraction of virtually all groups of exposed rats, and persisted at the longest post-exposure periods. These two manifestations of oxygen-induced retinopathy are emphasized because they lead to an abnormal separation of the retina from the epithelial layer, which may increase the likelihood of the most serious consequence of ROP--retinal detachment. In fact, all rats that endured post-exposure periods of 38 days or longer before sacrifice exhibited retinal detachment.

Animals↗
PubMed1990

Identification of GABAergic amacrine cell-like neurons developing in chick retinal monolayer cultures.

Purified neuronal monolayer cultures were prepared from embryonic chick retinae. Using immunocytochemistry for GABA and autoradiographic demonstration of [3H]muscimol uptake as markers, approximately 32% of the cells were identified as putative in vitro counterparts of gamma-aminobutyric acidergic (GABAergic) amacrine cells. Whole cell patch clamp recordings revealed close similarities between identified [3H]GABA accumulating neurons in culture and amacrine cells recorded in retinal slices, with respect to voltage-dependent membrane currents and to ion channels gated by exitatory (N-methyl-D-aspartate, kainate, quisqualate, glutamate) and inhibitory (GABA, glycine) amino acid agonists. The results demonstrate that retinal neurons are able to differentiate in dissociated retinal cultures. Such cultures may thus serve as a model system to study development and function of CNS neurons.

Animals↗
PubMed1985

Human fetal optic nerve: overproduction and elimination of retinal axons during development.

We have estimated the number of axons in the optic nerves of human fetuses ranging in gestational age from approximately 10 to 33 weeks. At 10-12 weeks of gestation there were an estimated 1.9 million axons in the optic nerve. A peak count of 3.7 million axons was obtained from a specimen of 16-17 weeks gestation. The estimated number of axons then declined, stabilizing at an estimated 1.1 million axons by about week 29 of gestation. This figure is in close agreement with an estimate of 1.1-1.3 million optic axons in the human adult optic nerve. The results indicate that at least 70% of optic axons generated during development of the primary visual pathway are lost during fetal life. Part of this loss probably occurs as a result of the refinement of the terminal distribution of ganglion cell projections within their target nuclei. The significance of the relatively prolonged period of axonal loss is discussed.

Axons↗
PubMed2001

Constant dark-rearing effects on visual adaptation of the zebrafish ERG.

Anatomical and electrophysiological studies have shown that zebrafish retinal neurons develop in a sequential manner. Several studies have examined the impact of restricted rearing environments on zebrafish visual development, but the results have been mixed. The purpose of this study was to examine the development of light adaptation properties of the zebrafish electroretinogram (ERG), and examine the effects of constant dark rearing on retinal development. Subjects were zebrafish, Danio rerio, reared under normal lighting conditions and zebrafish reared in constant dark from fertilization to 6 days postfertilization (dpf). Increment threshold functions were obtained from a- and b-wave ERG responses from normally reared subjects at different ages and from animals exposed to early constant dark rearing. Dark-reared subjects were tested immediately following constant dark exposure (6-9 dpf) and after exposure to normal cyclic lighting (11-13 dpf). Adult zebrafish were significantly more sensitive at lower background illuminations than were larvae zebrafish. Also, constant dark rearing had a differential effect on the a- and b-wave response measures. Constant dark rearing raised b-wave threshold uniformly across background illuminations, while only producing higher a-wave thresholds at low levels of illumination. These results are consistent with findings in studies on zebrafish retinal development, and may help explain some of the discrepancies across studies examining the effects of restricted rearing.

Aging↗
PubMed2000

Quantitative MR imaging study of intravitreal sustained release of VEGF in rabbits.

PURPOSE: To determine whether sustained elevation of vascular endothelial growth factor (VEGF) in the vitreous cavity causes retinal hyperpermeability [blood-retinal barrier (BRB) breakdown] before the development of retinal neovascularization (NV) and to document the kinetics of the integrity of BRB breakdown versus time. METHODS: Poly(L-lactide-co-glycolide)based devices loaded with VEGF were implanted intravitreally in rabbit eyes. Contrast-enhanced magnetic resonance imaging (MRI) methods were used to identify and quantitate the retinal permeability at various time points after implantation. This was done with the newly developed MR tracer AngioMARK (Epix Medical, Boston, MA). After the MRI measurements, fundus photography and fluorescein angiography (FA) also were performed on the same set of animals. RESULTS: At 3 days after implantation, the MR images showed a significant retinal leakage into the vitreous cavity (BRB breakdown) of the VEGF-implanted eyes. To quantitate this leakage, the permeability surface area product (PS) was measured. At 3 days, the mean PS product was 1.25 +/-0.25 x 10(-5) cm3/min. Based on the VEGF in vitro release study, this 3-day BRB breakdown corresponded to a total sustained release of 7.42 +/- 0.54 microg/ml of VEGF. The fundus and FA photographs of these VEGF-implanted eyes taken at 4 days after implantation also showed a considerable level of retinal vascular dilation and tortuosity. By 12 days after implantation, the mean PS product decreased to 5.83 +/- 1.38 x 10(-6) cm3/min. However, the retinal NV was observed only after the second week after implantation. By this time, a total of 10.70 +/- 0.92 microg/ml of VEGF was released in a sustained fashion. Also, after the retinal NV development, retinal detachment also was observed. The control eyes, however, which were implanted with blank devices, remained unchanged and normal during the entire course of this study (PS = 5.57 +/- 0.66 x 10(-7) cm3/min). CONCLUSIONS. The findings indicate that sustained delivery of elevated amounts of VEGF in the vitreous cavity induces a BRB breakdown even earlier than 3 days after implantation. This was achieved after a total sustained release of 7.42 +/- 0.54 microg/ml of VEGF. This retinal leakage regressed by more than half by the time the retinal NV developed. Furthermore, a retinal detachment occurred after this retinal NV. These results are similar to proliferative diabetic retinopathy (PDR). The sustained elevation of VEGF in the vitreous cavity of rabbit eyes is potentially a good model to test VEGF antagonists to treat or prevent PDR in humans. The quantifiable change of BRB breakdown by the contrast-enhanced MRI method is ideal to assess the therapeutic intervention in vivo without killing the animal and may prove to be clinically useful in humans.

Animals↗
PubMed2005

Creatine transporter localization in developing and adult retina: importance of creatine to retinal function.

Creatine and phosphocreatine are required to maintain ATP needed for normal retinal function and development. The aim of the present study was to determine the distribution of the creatine transporter (CRT) to gain insight to how creatine is transported into the retina. An affinity-purified antibody raised against the CRT was applied to adult vertebrate retinas and to mouse retina during development. Confocal microscopy was used to identify the localization pattern as well as co-localization patterns with a range of retinal neurochemical markers. Strong labeling of the CRT was seen in the photoreceptor inner segments in all species studied and labeling of a variety of inner neuronal cells (amacrine, bipolar, and ganglion cells), the retinal nerve fibers and sites of creatine transport into the retina (retinal pigment epithelium, inner retinal blood vessels, and perivascular astrocytes). The CRT was not expressed in Müller cells of any of the species studied. The lack of labeling of Müller cells suggests that neurons are independent of this glial cell in accumulating creatine. During mouse retinal development, expression of the CRT progressively increased throughout the retina until approximately postnatal day 10, with a subsequent decrease. Comparison of the distribution patterns of the CRT in vascular and avascular vertebrate retinas and studies of the mouse retina during development indicate that creatine and phosphocreatine are important for ATP homeostasis.

Animals↗
PubMedDate not supplied

Latest developments in treating retinal detachment.

Retinal detachment is a significant cause of blindness. Until the second quarter of this century, no successful treatment was available. Since then, there have been many exciting developments so that nowadays the majority of retinal detachments can be successfully repaired.

Cryosurgery↗
PubMed1975

The effects of early tectal lesions on development in the retinal gonglion cell layer of chick embryos.

The possibility that the arrival of retinal ganglion cell axons in their efferent target field could influence the subsequent progress of cytomorphogenesis in the ganglion cells was tested by destroying all or portions of the primordial optic tectum at four or five days of incubation. The lesions were made essentially prior to the outgrowth of axons from the eye. Complete bilateral or unilateral destruction of the primordial tectal field did not detectably alter the morphogenesis of the inner retina or of the ganglion cells until 11 days of incubation. After this time, extensive loss of ganglion cells occurred within the retinas contralateral to the projection fields that were destroyed. The cytology of this degeneration is described as seen with the light and electron microscope. After smaller lesions involving the anterior or posterior half-tectum on one side, however, variable results occurred both in tectal development and in the retinal locus of ganglion cell degeneration observed in flat mount preparations. Many partial or punctate lesions, in fact, resulted in no detectable loss of cells from the ganglion cell layer. These results are discussed in regard to specification and possible regulatory capabilities of the tectum. Cell death in normal retinas, not previously reported in the chick, is also considered in relation to the experimental results.

Animals↗
PubMed1988

The development of scotopic retinal function in human infants.

Scotopic retinal function undergoes age-related changes early in human infancy. Electroretinographic psychophysical, and pupillographic responses have been used in the study of normal development. Various components of the electroretinographic responses index distal and proximal retinal function. Changes in pupillary diameter, measurable in infants under carefully selected conditions, represent rhodopsin regeneration in the infants under carefully selected conditions, represent rhodopsin regeneration in the photoreceptor outer segment. From psychophysical data, inferences can be drawn about scotopic retinal control of visual performance. These data constrain theories about the determinants of sensitivity, about the flow of signals from the distal, rhodopsin-bearing, outer segments to the proximal retina, and about modulations of straight-through flow by feedback or inhibitory circuits. The results indicate that the post natal development of human scotopic function is due mainly to reorganization of processes central to the photoreceptors.

Adaptation, Physiological↗