Pigmented Epithelium Derived Factor (PEDF) prevents apoptosis and acts as a neurotrophic factor for retinal neurons

MICHELIS, G.; GERMAN, O.L.; ROTSTEIN, N.; POLITI, L.; BECERRA, P.

Congreso; SAN 2018; 2018

SAN

PEDF has been shown to be cytoprotective on the R28 retinal progenitor cell line, but its effects on retinal neurons remain largely unknown. We investigated its effects in cultured photoreceptors and amacrine neurons. Pure neuronal cultures from 1-day old rat retinas were grown in a serum-free, chemically defined media, and incubated at day 2 with PEDF, small fragments from its neurotrophic (44-mer and 17-mer) or antiangiogenic (34-mer) domains, PEDF plus the blocking peptide P1, the PEDF-Receptor (PEDF-R) inhibitor, atglistatin; or vehicle (control) for 3 days. Apoptosis, cell death, opsin expression and axonal outgrowth were then analyzed. PEDF and the fragments from its neurotrophic domain prevented apoptosis, preserving mitochondrial functionality, and promoted both opsin localization in photoreceptor apical ends and neurite outgrowth, mainly in amacrine neurons. Retina neurons expressed PEDF-R, which showed a high degree of colocalization with membrane markers. Pre-treatment with either P1 or atglistatin abolished PEDF effects whereas the fragment from PEDF antiangiogenic domain had no effect. In summary, this work suggests that PEDF is an effective survival factor for retinal photoreceptors during development in vitro. It also implies that PEDF plays different roles in neuronal differentiation, promoting the polarization and differentiation of photoreceptors and stimulating axonal outgrowth in amacrine neurons through the activation of its membrane receptor.