The role of retinal pigment epithelium in the involution of subretinal neovascularization

The extravascular milieu around laser-induced experimental subretinal neovascularization (SRN) was studied during the evolution of the neovascular membrane from its early leaky stage to its late involuted stage. When the first signs of visible leakage appeared on angiography, newly formed vessels were spread in the subretinal space around the break in Bruch's membrane, fluid was accumulating in the subretinal space, and retinal pigment epithelial (RPE) cells were proliferating in a papillary pattern around the newly formed vessels; the RPE proliferation began with the undamaged cells at the edges of the laser injury. With further maturation, the RPE continued to envelope the subretinal vessels. This RPE proliferation was associated with the disappearance of fluid between the enveloped vessels and the sensory retina, and the gradual cessation of fluorescein leakage during angiography. At the end of the involution process, when the neovascular membrane no longer demonstrated any leakage, the subretinal vessels were found to be tightly enveloped by RPE cells, and no fluid separated them from the sensory retina. The authors' results suggest that involution of the neovascular membrane with maturation, as demonstrated by the cessation of visible fluorescein leakage, is the result of RPE proliferation that tightly envelopes the newly formed vessels and probably resorbs the previously accumulated subretinal fluid, as well as preventing its further accumulation in the subretinal space.