Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration

PURPOSE: Pigment epithelium-derived growth factor (PEDF) is a potent inhibitor of angiogenesis that is found in the normal eye. The purpose of this study is to report decreased levels of PEDF in the vitreous of eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). DESIGN: Prospective case-control study. METHODS: In a prospective case-control study, undiluted vitreous was collected from nine eyes of nine patients with CNV due to AMD and from an age-matched control group of 12 eyes of 12 patients with retinal disorders not involving neovascularization. Vitreous PEDF and vascular endothelial growth factor (VEGF) concentrations were determined by Western blot analyses and enzyme-linked immunosorbent assay (ELISA), respectively. Angiogenic activities of the vitreous samples were assessed in vitro using an endothelial cell chemotaxis assay. RESULTS: In vitreous samples from nine eyes with CNV due to AMD the mean +/- SD PEDF level was 2.8 ng/microl +/- 1.3 ng/microl. In vitreous samples from 12 age-matched control eyes the mean +/- SD PEDF level was 16.4 ng/microl +/- 7.1 ng/microl. The difference between the two groups was statistically significant (P =.00003). No significant difference in vitreous VEGF concentration was seen between CNV/AMD samples and control samples (P =.23). All CNV/AMD vitreous samples induced endothelial cell migration in vitro. No sample from age-matched non-age-related macular degeneration controls could induce endothelial cell migration, and 11 of 12 were able to block VEGF-induced migration in vitro. This inhibitory activity required active PEDF. CONCLUSION: The vitreous of patients with CNV due to AMD contained lower levels of PEDF and lacked the antiangiogenic activity of vitreous from age-matched controls. This suggests that loss of PEDF creates a permissive environment for CNV patients with AMD.