Inhibition of choriocapillaris regeneration with genistein.

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Abstract

PURPOSE: To test the effects of genistein on choriocapillaris regeneration and retinal pigment epithelial (RPE) wound healing in a surgical model in the rabbit. METHODS: Intravitreal injections of either 0.1 ml of a 90-microM concentration of genistein, dimethyl sulfoxide (DMSO; negative control), or 2 microg cycloheximide (positive control) were given 24 hours before surgical debridement of RPE in rabbits. Scanning electron microscopy (EM) of choroidal vascular casts and the RPE wounds and histologic evaluation by light microscopy and EM of the disturbed areas were performed at days 1, 7, and 30 after surgery. Quantitative analysis of the area of the choriocapillaris bed and RPE was performed by automated image analysis, and the results were analyzed by paired Student's t-test. RESULTS: Loss of RPE caused a rapid initial atrophy followed by slower subsequent revascularization of the choriocapillaris, which paralleled the RPE wound healing. Choriocapillaris regeneration appeared nearly normal by day 30 in the DMSO group. Inhibition of choriocapillaris revascularization by genistein was significant at day 30 when compared with the DMSO-treated negative control (P = 0.013). There was a strong trend toward inhibition in the cycloheximide-treated positive control group (P = 0.062), which reached significance at day 7 compared with the DMSO group (P = 0.02). RPE covered the wound area by day 7 in all groups. CONCLUSIONS: Intravitreal injection of genistein was found to cause significant inhibition of choriocapillaris regeneration without apparent effect on RPE wound healing. Tyrosine kinase inhibitors such as genistein may be useful as a pharmacologic approach in the treatment of choroidal neovascularization.