Pigment Epithelium–derived Factor Promotes Differentiation of Immature Retinal Ganglion Cells

Abstract

Abstract: : Purpose: To analyze that PEDF promotes differentiation of immature retinal ganglion cells and MAPK pathways are activated through the differentiation Methods: Neuronal differentiation effects of PEDF were determined by quantifying the neurite length extending from cultured chick embryo retinal explants, and neuronal differentiation rate of R28 cells (a neural cell line derived from the neonatal rat retina). The MAPK activity levels were determined by inhibition assays. Quantification of the contribution of the signaling pathway was performed with specific inhibitors for MAPK; PD98059. Results: PEDF (50ng/ml) promoted chick retinal neurite elongation up to 196.2% and increased differentiation rate of R28 cells up to 163.5% respectively. PD98059 addition for 48 h decreased neurite elongation down to 75.7% and also decreased the differentiation rate of R28 cells down to 47.7% optimally at a concentration of 20µM and 5µM respectively. PEDF induced immature retinal cells differentiation through the MAPK pathway. Inhibition of MAPK with PD98059 blocked the ability of PEDF to promote neurite outgrowth of immature retinal ganglion cells. Conclusions: PEDF is a differentiation factor for immature retinal ganglion cells by activating MAPK pathways. These data suggest that PEDF provides useful support for retinal neurons through MAPK pathway and lead to progress in therapy for many retinal diseases.

Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • retinal development • retinal culture