Development of the human retina: Patterns of cell distribution and redistribution in the ganglion cell layer

Abstract

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.

Vascular endothelial growth factor in eye disease

“…Alternatively, those who believe that vasculogenic growth drives the formation of the primary network, contend that the process is not dependent on metabolic demand and physiologic hypoxia (Hughes et al, 2000). Their case is supported by several observations: 1) VEGF expression is not detected in the inner layers of the human retina until after the time when active retinal vasculogenesis has been observed (Provis et al, 1997); 2) vasculogenesis is established at about 15 weeks gestation, a period prior to active neuronal differentiation (Provis et al, 1985) and although neuronal maturation is highest in the perifoveal region during this period, this region is vascularized much later in gestation; and 3) although VEGF null mice are not viable and have abnormal blood vessels, vessel formation does occur in these animals (Carmeliet et al, 1996).…”

Ophthalmological problems associated with preterm birth

“…17 The neural retina emerges around 26 days gestation, with the inner layer of the optic vesicle undergoing mitosis producing three or four compact layers of cells. 18 Retinal development is centred around the putative macula and proceeds centroperipherally, 19 with mitotic activity being gradually confined to the periphery until 24 weeks of gestation when all mitosis ceases. The retinal surface area is still expanding, but does so by growth and maturation of individual cells until 3 weeks after birth.…”

Optic nerve axons: life and death before birth

“…47 Apoptosis or (genetically) programmed cell death plays an important role in the development of RGCs and their axons. [48][49][50][51] Recently, interest has been focussed on the process of perverted apoptosis that may occur in diseases such as glaucoma (Table 1). 52 Developing RGC axons in the chiasm Normal vision is dependent on ordered neuronal maps of visual space which depend on precise connections between retinal axons and their target cells.…”

“…49,50 The lumen of the optic stalk is initially open and in communication with the forebrain cavity. It closes by the end of the second month of gestation, when it elongates and the foetal fissure is formed.…”