Overstatement of Hepatocyte Growth Factor (HGF) in the Retinal Pigment Epithelium Induces the Development of Subretinal Membranes and Chronic Retinal Detachment

Abstract

Abstract: : Purpose:Hepatocyte growth factor (HGF) is a pleiotrophic growth factor that has been shown to regulate various functions of retinal pigment epithelial (RPE) cells. In this study, we investigated the effects of recombinant adenovirus-mediated overstatement of HGF on RPE cells in vivo. Methods:An E1/E3-deleted adenoviral vector encoding HGF (Ad CMV.HGF) was injected subretinally into the eyes of adult pigmented rabbits at a concentration of 5x104 pfu/eye. An adenoviral vector encoding green fluorescent protein (Ad CMV.GFP) was used as control. HGF statement was identified by immunohistochemistry. Histopathologic changes were determined by light and electron microscopy and immunohistochemistry. Results:Eyes injected with AdCMV.HGF showed HGF immunopositivity in RPE cells adjacent to the injection site, whereas control eyes injected with an equivalent dose of AdCMV.GFP showed no HGF staining. Eyes injected with control vectors showed that GFP statement was located predominantly in the RPE monolayer with minimal morphological changes. Eyes injected with Ad CMV.HGF showed chronic retinal detachment with subretinal membranes composed of depigmented RPE and chronic inflammation in the choroid. Conclusion:These data support our hypothesis that HGF is a critical factor in the early stages of PVR pathogenesis.

Keywords: 563 retinal detachment • 316 animal model • 567 retinal pigment epithelium