Development of the retinal vasculature

Abstract

Blood vessels that supply the inner portion of the retina are extensively reorganized during development. The vessel regression, sprouting angiogenesis, vascular remodelling and vessel differentiation events involved critically depend on cell-cell signalling between different cellular components such as neurons, glia, endothelial cells, pericytes and immune cells. Studies in mice using transgenic and gene deletion approaches have started to unravel the genetic basis of some of these signalling pathways and have lead to a much improved understanding of the molecular mechanisms controlling retinal blood vessel behaviour both during development and under pathological conditions. Such insight will provide the basis of future therapeutic approaches aimed at manipulating retinal blood vessels.

Vascular endothelial growth factor in eye disease

“…The vessels of the hyaloid extend from their source at the optic nerve head to the posterior surface of the lens, where they bifurcate to form the dense capillary arbor known as the tunica vasculosa lentis. This network regresses during mid-gestation in the human and two to three weeks post-natally in the mouse and rat, coinciding with the period of retinal vascular development (Gogat et al, 2004;Fruttiger, 2007).…”

“…There is a close correlation between migration of retinal astrocytes, expression of VEGF and development of the superficial vascular plexus; the avascular fovea in humans does not contain astrocytes (Chan-Ling et al, 1992;Holash and Stewart, 1993;Gariano et al, 1994;Jiang et al, 1994;Sandercoe et al, 1999;Dorrell et al, 2002;Fruttiger, 2007). Initially, superficial blood vessels follow the central to peripheral gradient of retinal astrocyte maturation towards the periphery of the retina, which is reached by P8 in mice, P12 in rats and 32 weeks gestation in the human.…”

“…These vessels sprout from the superficial plexus and extend into the deeper layers of the retina, forming the deep vascular plexus. CD34 staining, confirmatory for endothelial cells, demonstrates that the increase in vascular density of the superficial plexus and the growth of the deep plexuses occur by angiogenesis (Hughes et al, 2000;Fruttiger, 2007). In the human fetus, this process begins around 25 weeks gestation, simultaneous with the appearance of the visual evoked potential (Leaf et al, 1995;Hughes et al, 2000;Dreher and Robinson, 1998;).…”

“…Scale bars are 100 μm. Adapted from Fruttiger, 2007. P6 mice were exposed to 20% (A), 40% (B) or 80% (C) oxygen for 36 hours.…”

Special features of human retinal angiogenesis

“…1,3 In mice, a series of reciprocal interactions between ganglion cells, astrocytes, and vessels has been described, which suggest that ganglion cells and astrocytes provide a blueprint for subsequent retinal vascularization. 5 In brief, ganglion cells stimulate glial growth by release of PDGF-A that exerts an effect on astrocytic receptors to provide attractant and mitotic cues. Astrocytes thus extend roughly along axonal lines but proliferate and spread out by contact spacing to form a honeycombed meshwork of cells and processes.…”