Cell death and the elimination of retinal axons during development.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J M Provis
Publications and source records attributed to J M Provis.
Class-specific cell death shapes the distribution and pattern of central projection of cat retinal ganglion cells.
The development of the nasotemporal division in cat retina was studied. We find that in the normally pigmented neonatal cat significant numbers of ganglion cells of all types in temporal retina project to the contralateral dorsal lateral geniculate nucleus (LGNd); far fewer cells in temporal retina project contralaterally to the LGNd in the normal adult. Thus, most of these cells must be eliminated during development. Experimental interruption of one optic tract in the neonate results in the retrograde degeneration of the ipsilaterally projecting ganglion cells in the temporal retina ipsilateral to the lesion. Consequent to the loss of the ipsilaterally projecting cells in this hemiretina, many of the ganglion cells projecting to the intact contralateral LGNd, which are normally eliminated, survive. Also, unlike in the normal cat, in which very few of the small ganglion cells in temporal retina project contralaterally to the thalamus, in optic tract sectioned (OTX) cats, significant numbers of the smallest ganglion cells in the temporal retina ipsilateral to the lesion project contralaterally to the intact thalamus. In order to make a quantitative comparison of the distributions of ipsilaterally and contralaterally projecting cells in the temporal retinae of normal cats, OTX cats, and neonatal kittens, it was necessary to determine the position of the vertical meridian in all animals. We defined the vertical meridian as the median edge (Stone, 1966). The median edge was determined from the distribution of the most nasally located, ipsilaterally projecting cells in temporal retina. The results indicate that the angle of the vertical meridian (median edge) with respect to the area centralis and optic disc is specified before birth and does not differ in normal cats, OTX cats, or neonatal kittens. Since the location of the vertical meridian does not change with age in postnatal life and is not affected by optic tract section, corresponding regions of retina in the different groups could be compared. A quantitative analysis of ganglion cell density in the temporal retina contralateral to the section, ipsilateral to the intact hemisphere, indicated that there was a reduction in the population of ipsilaterally projecting ganglion cells that was complementary to the abnormally large number of contralaterally projecting cells surviving in the temporal retina ipsilateral to the lesion.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Patterns of cell death in the ganglion cell layer of the human fetal retina.
The distribution of dying cells in the ganglion cell layer (GCL) of retinae from human fetuses has been analysed. Both whole-mounted and sectioned retinae have been studied. Results suggest that cells are lost from the GCL between weeks 14 and 30 of the gestation period, approximately. This period corresponds to the period during which axons are lost from the developing optic nerve. Cell loss is greatest between weeks 16 and 21 of the gestation period. The pattern of cell loss is nonuniform, and between weeks 16 and 24, the relative frequency of pyknotic cells (pyknotic cells:viable cells) in peripheral retina is considerably higher than in central retina. This pattern of cell loss predominates during the period in which a distinct centroperipheral gradient of cell densities emerges in the GCL of the human fetal retina (between 18 and 23 weeks gestation). It is suggested that the regional loss of ganglion cells may contribute to the formation of the cell density gradient.
Cell Count↗
Age-related macular degeneration: ultrastructural studies of the relationship of leucocytes to angiogenesis.
We describe the ultrastructural features of subretinal neovascularisation associated with the pathogenesis of age-related macular degeneration (AMD). The choroidal origin of new vessels was confirmed, and ultrastructural details are presented. Serial sectioning of new vessels revealed a relationship between leucocytes and neovascular structures. The results are discussed in the context of the previously established role of leucocytes in angiogenesis. Our results provide circumstantial evidence, based on morphological observations, for the involvement of leucocytes in the promotion of neovascular proliferation and exudation from new vessels.
Aged↗
Cell death in the development of the human retina: phagocytosis of pyknotic and apoptotic bodies by retinal cells.
Apoptosis is a natural form of cell death and has features in common with aspects of cell deletion observed in the course of human retinal development. In this report, we describe the occurrence of apoptotic cells in various layers of the developing retina. Pyknotic residues were observed within phagosomes of neighbouring retinal cells. Our observations imply that most of the debris resulting from cell death is taken up by adjacent tissue cells rather than by mononuclear phagocyte series cells (macrophages) during early stages of human retinal development.
Cell Nucleus↗
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↗
Development of the human retina: patterns of cell distribution and redistribution in the ganglion cell layer.
Neurogenesis in the ventricular layer and the development of cell topography in the ganglion cell layer have been studied in whole-mounts of human fetal retinae. At the end of the embryonic period mitotic figures were seen over the entire outer surface of the retina. By about 14 weeks gestation mitosis had ceased in central retina and differentiation of photoreceptor nuclei was evident within a well-defined area which constituted about 2% of total retina area. This area was approximately centered on the site of the putative fovea, identified by the exclusive development of cone nuclei at that location. The area of retina in which mitosis had ceased increased as gestation progressed. By mid-gestation mitosis in the ventricular layer occupied about 77% of the outer surface of the retina and by about 30 weeks gestation mitosis in the ventricular layer had ceased. Cell density distributions in the ganglion cell layer were nonuniform at all stages studied (14-40 weeks). Densities were highest at about 17 weeks gestation, and by mid-gestation the adult pattern of cell topography was present with maps showing elevated cell densities in posterior retina and along the horizontal meridian. Cell densities generally declined throughout the remainder of the gestation period, except in the posterior retina, where densities in the perifoveal ganglion cell layer remained high during the second half of gestation. There is a rapid decline in cell density in the foveal ganglion cell layer toward the end of gestation, and it is suggested that the persistence of high densities in the perifoveal region may be related to migration of cells away from the developing fovea. The total population of cells in the ganglion cell layer was highest (2.2-2.5 million cells) between about weeks 18 and 30 of gestation. After this the cell population declined rapidly to 1.5-1.7 million cells. It is suggested that naturally occurring neuronal death is largely responsible for this decline.
Cell Count↗
Retinal development in humans: the roles of differential growth rates, cell migration and naturally occurring cell death.
The distribution of ganglion cells throughout the retinal ganglion cell layer is non-uniform in adult mammals. This paper reviews some of our data describing the development of retinal ganglion cell topography in the human fetus. Results indicated that early in the fetal period the distribution of cells in the ganglion cell layer is almost uniform, but by the end of gestation there is a gradient in cell density of about 10:1 (central:peripheral). Peripheral retina grows more rapidly than the central retina prior to about 23 weeks gestation, but this differential growth rate apparently has little effect on the development of a centro-peripheral density gradient. The gradient appears between about 18 and 30 weeks gestation, and during this period there appears to be a greater rate of cell death in the ganglion cell layer of the peripheral retina. Cell density at the developing fovea is less than the perifoveal cell density at all ages, suggesting that ganglion cells migrate from foveal into perifoveal regions throughout the fetal period.
Cell Count↗
Visual deprivation in infancy and childhood: clinical aspects.
The effects of visual deprivation in 15 patients (14 children and one adult) were studied. The age of onset of deprivation and the significance of final visual outcome are discussed. Results indicate that a critically sensitive period in visual development occurs between approximately four months and three years of age. A period of plasticity, when the effects of deprivation are more responsive to therapy, follows. Age of onset of deprivation was found to be most important, but in addition loss of accommodation in association with deprivation may be a significant factor in the development of amblyopia.
Adult↗
Ganglion cell topography in human fetal retinae.
Whole-mounted human fetal retinae of gestational ages 14-40 weeks have been studied. These preparations clearly show the distribution of retinal ganglion cells or their precursors across the retina, and the pattern of the retinal vessels and vessel primordia. The ganglion cell layer is present at 14 weeks of gestation and distribution of cells in this layer (ganglion cell precursors) is at first uniform. Ganglion cell density gradients that foreshadow those seen in the adult retina become evident by about 20 weeks gestation. Both mature ganglion cells and precursor cells are present in retinae at about 24 weeks and precursor cells are still seen in the peripheral parts of the retina at about 30 weeks of gestation. The development of mature ganglion cells would appear to coincide with the establishment of retinal circulation, and proceeds in centrifugal sequence from central retinal.
Gestational Age↗
The distribution of ipsilaterally and contralaterally projecting ganglion cells in the retina of the pigmented rabbit.
The retinal distribution of ipsilaterally and contralaterally projecting ganglion cells has been determined in the rabbit using both degeneration and horseradish peroxidase tracing techniques. Contralaterally projecting ganglion cells are present throughout the retinas, while ipsilaterally projecting ganglion cells are confined to a 3.0-3.5 mm wide strip adjacent to the temporal retinal margin. Thus, in this temporal strip both ipsilaterally and contralaterally projecting cells intermingle, while at more nasal locations all ganglion cells project contralaterally. Each of the contra- and ipsilaterally projecting populations comprises ganglion cells with soma diameters representing the full range present in the rabbit retina. However, a relatively large proportion of the ipsilaterally projecting ganglion cells have large somata (greater than or equal to 20 micrometer). Large ganglion cells are most numerous in the rabbit's temporal retina and have previously been described as reaching their peak density at the large cell node, just above the temporal end of the visual streak (Provis 1979). The large cell node lies immediately temporal to the nasal border of the strip of retina in which ipsilaterally projecting cells are located. It is possible that this specialization in the region of retina which observes the binocular visual field plays a particular role in binocular vision for the rabbit.
Afferent Pathways↗
The distribution and size of ganglion cells in the regina of the pigmented rabbit: a quantitative analysis.
The distribution and soma diameters of retinal ganglion cells have been examined in whole mounted retinae of pigmented rabbits. Maps of the distribution of ganglion cells confirmed several features of earlier descriptions, but generally showed lower density values and yielded lower total ganglion cell counts (250,000-270,000). The maximum ganglion cell density encountered in each retina and its retinal location both varied between rabbits. As previously reported, the dominant feature of the rabbit's retina is a strongly developed visual streak (Hughes, '71) but some evidence of an area centralis-like specialization was found. This appears not as the area of peak gangion cell density, but as a concentration of large (greater than or equal to 20 micron in diameter) ganglion cells at the temporal end of the visual streak, 2-3 mm from the temporal margin of the retina. In one rabbit in which the optic tract was sectioned five months previously, the density distribution of large retinal ganglion cells in the retinae has been mapped. These maps indicate that the nasotemporal division for large ganglion cells in the rabbit retina is approximately centered on the area of their maximum density. It has previously been reported that in the cat the area centralis is characterized by an aggregation of smaller diameter ganglion cells of a particular functional type (Stone, '65, '78). It is possible that areas of retinal which subserve area centralis-like functions are represented not simply by localized increases in ganglion cell density, but by changes in the relative proportions of ganglion cell types, which are reflected in the changing relative densities of ganglion cell soma diameter groups.
Animals↗