The role of estrogen and estrogen receptorbeta in choroidal neovascularization.
OBJECTIVE
Choroidal neovascularization (CNV) under the age of 50 is more often observed in women than in men. The effects of 17beta-estradiol (E2) on choroidal neovascularization development were investigated both in animal models and cultured cells to see if estrogen receptors (ERs) are involved in the process.


METHODS
CNV was induced by fundus laser photocoagulation in adult male and female rats. The degree of CNV development was scored and compared between them. Gene expression levels of VEGF receptor 2 (VEGFR2) and ERs after photocoagulation were compared between genders using real time PCR. CNV formation and the gene expressions were also examined in ovariectomized females with and without E2 treatment. The roles of ERs were studied by overexpressing them in human umbilical vein endothelial cells (HUVECs). The localization of estrogen receptorbeta (ERbeta) and VEGFR2 in CNV were studied immunohistochemically.


RESULTS
CNV scores were significantly higher in females than in males 14 and 21 days after photocoagulation (<0.05). VEGFR2 and ERbeta gene levels were increased more in females than in males on day 7 (3.4 fold compared to 1.8 fold) and on day 3 (5.8 fold compared to 2.3 fold) after photocoagulation, respectively. Both ERbeta and VEGFR2 gene expressions were additively enhanced by photocoagulation and E2 treatment in ovariectomized females. E2 significantly enhanced VEGFR2 gene expression and cell proliferation in HUVECs overexpressing ERbeta. ERbeta and VEGFR2 are well co-localized in CNV tissue.


CONCLUSIONS
Estrogen may promote CNV development by increasing VEGFR2 gene expression via ERbeta.
Tanemura
Mai
M
Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Miyamoto
Noriko
N
Mandai
Michiko
M
Kamizuru
Hiroshi
H
Ooto
Sotaro
S
Yasukawa
Tsutomu
T
Takahashi
Masayo
M
Honda
Yoshihito
Y
D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000502:physiology*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005451:Fluorescein Angiography; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000502:physiology; D005822:Genetic Vectors; D017075:Laser Coagulation; D008297:Male; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D012737:Sex Factors; D014162:Transfection; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger; D004958:Estradiol; D040301:Vascular Endothelial Growth Factor Receptor-2