Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal

Dysfunction of the retinal pigment epithelium (RPE), its loss, or separatio n from the underlying neural retina results in severe photoreceptor degener ation. Pigment epithelium-derived factor (PEDF) is a glycoprotein with repo rted neuroprotective and differentiation properties that is secreted in abu ndance by RPE cells. The "pooling" of PEDF within the interphotoreceptor ma trix places this molecule in a prime physical location to affect the underl ying neural retina. The purpose of this study was to analyze the morphogene tic activity of PEDF in a model of photoreceptor dysmorphogenesis induced b y removal of the RPE. Eyes were dissected from embryonic Xenopus laevis, an d the RPE was removed before culturing in medium containing PEDF, PEDF plus anti-PEDF antibodies, or medium alone. Control retinas were maintained wit h an adherent RPE. Light and electron microscopic analysis was used to exam ine retinal ultrastructure. Opsin was localized immunocytochemically and qu antified as an index of outer segment membranous material and photoreceptor protein expression. Removal of the RPE resulted in an aberrant assembly of photoreceptor outer segments, loss of fine subcellular ultrastructure in p hotoreceptors, and a reduction in opsin protein levels when compared with c ontrol retinas. The addition of PEDF prevented the dysmorphic photoreceptor changes induced by RPE removal. In particular, photoreceptor ultrastructur e, outer segment membrane assembly, and steady-state levels of opsin were e quivalent to control conditions. Anti-PEDF antibodies completely blocked th e morphogenetic activity of PEDF. These results indicate that PEDF is able to mimic the supportive role of the RPE on photoreceptors during the final stages of retinal morphogenesis.