Development of the primate retinal vasculature

Human and macaque retinae have similar retinal vascular anatomy. The genera l features of the retinal vascular anatomy of these two primates have much in common with more widely studied animal models such as rat and cat. Howev er, primates are unique amongst mammals in having a region in temporal reti na specialized for high visual acuity, which includes the fovea centralis ( or 'fovea'). Several features distinguish the fovea from other parts of the retina, including a very high local density of cone photoreceptors, a high density of inner retinal cells during development, and an absence of retin al blood vessels. The retinal vascular complex comprises a number of cell types, in addition to vascular endothelial cells, including pericytes, microglia, astrocytes- none of which is intrinsic to the retina. In addition, amacrine-like cells make bouton-like associations with retinal vessels and may be involved in t he autoregulation of blood flow. During development endothelial cells 'inva de' the retina, accompanied by a population of microglial cells; glial fibr illary acidic protein (GFAP)immunoreactive astrocytes are also seen associa ted with the developing vasculature, and are in advance of the vascular fro nt by a few hundred microns, Recent findings indicate that astrocytes at th e vascular front proliferate in response to factors released by endothelial cells, including leukemia inhibitory factor. Better understood is the role of G FA-P-immunoreactive astrocytes just in advance of the developing vess els. These astrocytes are sensitive to hypoxia and in response release vasc ular endothelial growth factor (VEGF) which in turn promotes the migration, differentiation and proliferation of vascular endothelial cells. This hypo xia/VEGF-mediated process of migration, proliferation and differentiation a ppears common to the retinae of a variety of species, including human. Howe ver, in human and macaque retina, different mechanisms appear to govern the development of the retinal vessels growing along the horizontal meridian o f the retina towards the central area, which contains the fovea. Despite th e relatively advanced state of differentiation and maturation of cells in t he central area compared with the periphery, the growth of retinal vessels into the central area has been described as 'retarded', and the incidence o f cell proliferation associated with these vessels is lower than in periphe ral vessels. Furthermore, neither retinal vessels nor their accompanying as trocytes grow into a circumscribed region which, at a later stage, develops into the foveal depression. These observations suggest that molecular mark ers define the foveal region and inhibit cell proliferation and vascular gr owth at the fovea and, perhaps, along the horizontal meridian. The findings also suggest that at the fo ea, the retina is adapted morphologically to i ts blood supply, since in the vicinity of the fovea, the development of ret inal vessels is retarded or inhibited. The limitations on vascularization o f central retina has implications for its vulnerability to degenerative cha nges, as seen in age-related macular degeneration. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.