Pigment epithelium-derived factor delays the death of photoreceptors in mouse models of inherited retinal degenerations

Pigment epithelium-derived factor (PEDF) is a member of the serine protease inhibitor superfamily produced by retinal pigment epithelial cells in the developing and adult retina. In vitro, it induces neuronal differentiation of retinoblastoma cells and promotes survival of cerebellar granule neurons . The pedf gene is closely linked to an autosomal-dominant locus for retini tis pigmentosa, suggesting that PEDF could be a survival factor for photore ceptors. We have investigated this possibility by injecting PEDF into the e yes of homozygous retinal degeneration (rd) and retinal degeneration slow ( rds) mice, two mutants displaying apoptotic photoreceptor loss. This proced ure resulted in a transient delay of photoreceptor loss in the rd mouse and a reduction in apoptotic photoreceptor profiles in the rds mouse. We concl ude that PEDF can act as a survival-promoting factor for photoreceptors in vivo and could potentially be useful for the treatment of photoreceptor dis eases. (C) 1999 Academic Press.