An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris

Abstract

Clinical and experimental observations indicate a role for VEGF secreted by the retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris (CC). VEGF in mice is produced as three isoforms, VEGF120, VEGF164, and VEGF188, that differ in their ability to bind heparan sulfate proteoglycan. RPE normally produces the more soluble isoforms, VEGF120 and VEGF164, but virtually no VEGF188, reflecting the fact that molecules secreted by the RPE must diffuse across Bruch's membrane (BrM) to reach the choriocapillaris. To determine the role of RPE-derived soluble VEGF on the choriocapillaris survival, we used mice that produce only VEGF188. VEGF188/188 mice exhibited normal choriocapillaris development. However, beginning at 7 months of age, we observed a progressive degeneration characterized by choriocapillaris atrophy, RPE and BrM abnormalities, culminating in areas of RPE loss and dramatic choroidal remodeling. Increased photoreceptor apoptosis in aged VEGF188/188 mice led to a decline in visual acuity as detected by electroretinogram (ERG). These changes are reminiscent of geographic atrophy (GA) and point to a role for RPE-derived VEGF in the maintenance of the choriocapillaris.age-related macular degeneration ͉ Bruch's membrane ͉ geographic atrophy ͉ retinal pigmented epithelium

Is there a relationship between outer retinal destruction and choroidal changes in cone dystrophy?

“…Destruction of the RPE cells has been reported in animal models of disease responsible for secondary choriocapillaris atrophy (5,11) . A requirement for vascular endothelial growth factor, which is produced by RPE cells, has been demonstrated for choroidal maintenance; therefore, this growth factor may play a role in choroidal thinning (4,12) . The retinas, and especially the photoreceptor cells, are the most metabolically active tissues in the body, and their oxygen consumption is faster than that seen in other tissues (13) .…”

Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration

“…VEGF has been found to be produced constitutively by RPE cells, 43 and was increased in response to MAC formation on primary RPE cells. 44 Sustained low level secretion of VEGF is believed to be necessary for the normal development and maintenance of the choriocapillaris, 45 whereas on the other hand, pathological increases in VEGF contribute to several ocular diseases including neovascularisation in wet AMD. 46 Given that RPE cell-cell contacts may become disrupted in AMD, our findings therefore potentially link complement activation and sub-lytic MAC formation to increased VEGF secretion, and the neovascular processes observed in late stage disease.…”

Shared Triggering Mechanisms of Retinal Regeneration in Lower Vertebrates and Retinal Rescue in Higher Ones

“…In particular, it was shown that PEDF can act as an antiangiogenic factor that inhibits endothelial cell proliferation in the choriocapillaris. VEGF is another vasoactive factor of RPE known as preventing endothelial cell apoptosis (Saint-Geniez et al, 2009). In a healthy eye, PEDF and VEGF are secreted at opposite sides of the RPE cell.…”