Estrogen May Enhance Laser-induced CNV Formation by Enhancing VEGFR2 Gene Expression

Abstract

Abstract: : Purpose:Choroidal neovascularization (CNV) under the age of 50 mainly represented by idiopathic CNV and myopic CNV are more often observed in women than in men. We previously showed that 17beta estradiol(E2) has a positive effect on retinal endothelial proliferation. In the present study, using the rat CNV model induced by laser photocoagulation we studied the gender difference in susceptibility to CNV development. We also studied how E2 may be involved in the pathogenesis of CNV Methods:Fundus laser photocoagulation was performed to induce CNV in adult male and female rats and the CNV formation was evaluated by scoring fluorescein angiograms 7,14 and 21 days after photocoagulation. Gene expression levels of VEGF-receptor 2 (VEGFR2), estrogen receptors alpha and beta after laser photocoagulation were compared using semi-quantitative RT-PCR between male and female rats, and also in ovarectomized females with and without E2 treatment. The localization of proliferating cells, ER-beta positive cells, VEGFR2 positive cells in CNV were also studied using immunohistochemistry. Results:CNV scores were significantly higher in female than in male rats 14 and 21 days after laser photocoagulation (p<0.05). VEGFR2 gene level was more increased in females than in males 7 days after photocoagulation (11 fold vs 6 fold). ER-beta gene level was also increased more significantly in females (6 fold vs 2.3 fold on day3) whereas ER-alpha gene expression level remained constant in both sexes throughout the observation period. Both the ER-beta and VEGFR2 gene expressions were additively enhanced by laser photocoagulation and estradiol treatment. Conclusions:Estrogen may enhance CNV formation by enhancing VEGFR2 gene expression, and induction of ER-beta may play some role in the process. Our result may explain the more often occurrence of CNV in female patients than in male patients under the age of 50.

Keywords: choroid: neovascularization • gene/expression