Pigment Epithelium-derived Factor Inhibits Neuroretinal Apoptosis in a Murine Model of Focal Retinal Degeneration

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NEI	CLIN/TRANS-24

Authors

• Y. Wang
• D. Shen
• J. Tuo
• P. Subramanian
• S. P. Becerra
• C. C. Chan

Abstract

Purpose: Retinal cell apoptosis plays a critical role in age-related macular degeneration (AMD). Pigment epithelium-derived factor (PEDF) is proven to protect retinal cell death. We evaluated PEDF effects on Ccl2-/-/Cx3cr1-/- on Crb1rd8 background (DKO rd8) AMD mouse model. Methods: The right eyes of 6-week-old mice were intravitreously injected with recombinant human PEDF (1 µg), followed by a subconjunctival PEDF (3 µg) injection 4 weeks later. The left eyes were untreated as controls. Fundoscopic pictures were scored before injection and after injections. Ocular histopathology, retinal A2E and apoptosis molecules were assessed 4 weeks after the second injection. Results: Fundoscopy showed slower progression/attenuation of the retinal lesions in PEDF treated eyes than controls. Among 24 pairs of eyes, average clinical scores of progression are 1.14±0.12 in treated eyes and 1.32±0.14 in controls (p=0.08). Histology confirmed fewer/smaller photoreceptor lesions in treated eyes than controls. A2E was lower in treated eyes than controls (14±1.3 vs 21.3±1.6, p<0.01). There were higher Bcl2 and lower Bax and FasL in treated eyes than controls. Conclusions: PEDF may stabilize photoreceptor degeneration in DKO mice. One of the protective mechanisms may be via anti-apoptotic pathway. The neuroprotective effect of PEDF represents a novel approach for potential AMD treatment.

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