Role of Pigment Epithelium-Derived Factor (PEDF) in Photoreceptor Cell Protection

Pigment epithelium-derived factor (PEDF), a 50-kDa glycoprotein, was first isolated from medium conditioned by human fetal retinal pigment epithelial (RPE) cells and was shown to be made in vivo by both fetal and adult RPE cells. After release from the RPE, PEDF binds to the glycosaminoglycans of the interphotoreceptor matrix,1,2 placing it in a prime physical location to affect the underlying neural retina. The PEDF gene has been cloned, sequenced and shown to have a tight linkage with a retinitis pigmentosa locus (RP13) on chromosome 17pl3.3 making it a candidate gene for this form of retinal degeneration.3,4 It has been reported that PEDF supported normal development of photoreceptor neurons and opsin expression after retinal pigment epithium removal.5 PEDF acts as a survival factor for cultured cerebellar granule cells,6, 7, 8 spinal motor neurons,9,10 hippocampal neurons11 and recently we demonstrated the survival-promoting activity of PEDF on retinal neurons in vitro 12. In addition to its effects on neurons, PEDF is a potent anti-angiogenesis factor,13 and is considered as a key coordinator of retinal neuronal and vascular functions.14 However, the role of PEDF as a neuroprotective factor in the retina and its association with specific retinal degenerative diseases are still being elucidated. The aim of the present research is to examine whether PEDF can prevent or delay photoreceptor degeneration. Using H2O2-induced cell death in cultured retinal neurons as in vitro model and the light-dependent degeneration of rat photoreceptor cells as in vivo model, our data demonstrate that PEDF results in significant protection of photoreceptor cells.