Pigment Epithelium–Derived Factor Inhibits bFGF–Induced Corneal Neovascularization in Mice

Abstract

Abstract: : Purpose: Angiogenesis is an important pathogenic process in inflammatory and immunologic conditions involving the cornea. Pigment epithelium–derived factor (PEDF) has been found to inhibit neovascularization (NV) in various tissue beds. Our objective in this study is to characterize the ability of PEDF to inhibit corneal NV induced by basic fibroblast growth factor (bFGF or FGF–2) using a corneal micropocket assay in mice. Methods: Three groups of C57BL/6 mice were surgically implanted with a hydron polymer–based pellet into a corneal micropocket, using a modification of the technique described by Kenyon et al (IOVS 1996;37:1625–32). The pellet contained either bFGF and Sucralfate (group 1, n = 10), bFGF, PEDF, and Sucralfate (group 2, n = 10), or phosphate buffered saline (PBS) and Sucralfate (control group, n = 10). On day 5 after implantation, eyes were photographed using a digital camera (Nikon Coolpix 990, Nikon Inc., Melville, NY) and a 17X macro lens. Two parameters were used to assess corneal NV: the maximal vessel length (VL) extending from the limbal vasculature towards the pellet, and the contiguous circumferential zone of NV (clock hours of NV, where 1 clock hour equals 30 degrees of arc). The area of NV was then calculated as described by Kenyon et al (Exp Eye Res 1997;64:971–8). Results: Consistent with previous observations, bFGF implantation produced a vigorous neovascular response in all eyes. Addition of PEDF to the pellet resulted in a significantly reduced area of NV when compared to bFGF alone (p<0.05). The difference in area of NV between the control and the combined PEDF/bFGF groups was not statistically significant. One mouse developed an infectious corneal ulcer and was not included in statistical analysis. Conclusions: In this mouse micropocket model, PEDF has a significant inhibitory effect on bFGF–induced corneal NV. PEDF may represent a potential treatment modality for corneal neovascular disorders. Further studies relating to alternative methods of PEDF delivery are in progress.

Keywords: neovascularization • cornea: basic science • anterior segment