Abstract
Abstract: :
Purpose:Retinal pigment epithelial (RPE) cells may influence ocular angiogenesis, in both inhibitory or stimulatory ways. They produce the pigment epithelium-derived factor (PEDF), a potent anti-angiogenic molecule, and also VEGF, the known pro-angiogenic factor. In an ex vivo retinal explant model, we identified a yet unknown mechanism by which RPE may influence the course of the angiogenic process. Methods:We cultivated human retinal fragments in gels made from 1.54 mg/ml fibrin in autologous vitreous fluid supplemented with growth factors (150 ng/ml VEGF and 50 ng/ml bFGF). Results:After a week, we found that a population of pigment-loaded cells started to proliferate, and to invade the surrounding matrix. In about two weeks, these cells were sometimes closely followed or accompanied by capillary-like primordia. This association was reminiscent of the recently described intercellular cooperation between monocytes/macrophages and developing capillaries, which consists in formation of tunnels and in their likely colonization by endothelial cells, or by circulating endothelial precursors (Moldovan et al., Circ. Res., 2000, 87: 378). Conclusion:: Our data suggest that since RPE normally behave like macrophages by engulfing photoreceptor debris, their function may be diverted towards tunneling of the extracellular matrix when they leave their assigned anatomical location, as it may happen in age-related macular degeneration. This may be an additional contribution of RPE to the facilitation of angiogenesis in pathologic settings, which would overbalance their anti-angiogenic function.
Keywords: 483 neovascularization • 513 phagocytosis and killing • 308 age-related macular degeneration