The role of estrogen and estrogen receptorβ in choroidalneovascularization

[摘要] Purpose: Choroidal neovascularization (CNV) under the age of 50 ismore often observed in women than in men. The effects of17β-estradiol (E2) on choroidal neovascularization development wereinvestigated both in animal models and cultured cells to see if estrogenreceptors (ERs) are involved in the process.Methods: CNV was induced by fundus laser photocoagulation in adultmale and female rats. The degree of CNV development was scored andcompared between them. Gene expression levels of VEGF receptor 2(VEGFR2) and ERs after photocoagulation were compared between gendersusing real time PCR. CNV formation and the gene expressions were alsoexamined in ovariectomized females with and without E2 treatment. Theroles of ERs were studied by overexpressing them in human umbilical veinendothelial cells (HUVECs). The localization of estrogen receptorβ(ERβ) and VEGFR2 in CNV were studied immunohistochemically.Results: CNV scores were significantly higher in females than inmales 14 and 21 days after photocoagulation (<0.05). VEGFR2 andERβ gene levels were increased more in females than in males on day7 (3.4 fold compared to 1.8 fold) and on day 3 (5.8 fold compared to 2.3fold) after photocoagulation, respectively. Both ERβ and VEGFR2gene expressions were additively enhanced by photocoagulation and E2treatment in ovariectomized females. E2 significantly enhanced VEGFR2gene expression and cell proliferation in HUVECs overexpressing ERβ.ERβ and VEGFR2 are well co-localized in CNV tissue.Conclusions: Estrogen may promote CNV development by increasingVEGFR2 gene expression via ERβ.

[学科分类] 生物化学/生物物理