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DC Monroy, DG Espinosa, JM Legra, E Hernandez, KG Csaky, SW Cousins; The Role of Estrogen Status and Lesion Severity in Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1295.
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Purpose: Several retrospective clinical studies suggest that post-menopausal women may be at risk for more severe age-related macular degeneration (AMD), and that estrogen loss due to menopause may contribute. We sought to determine the effect of gender and estrogen status on the severity of choroidal neovascularization (CNV) in a mouse model. Methods: Laser induced CNV was performed in either male or female 9 month-old C57BL/6 mice. Another group of female mice underwent ovariectomy with or without estrogen supplementation using a sustained release pellet with 17 ß-estradiol. Two or 4 weeks post-laser, mice were injected intravenously with fluoresceinated dextran. The right eyes were removed and prepared for flatmount analysis of CNV surface area (in disc areas or DA), vascularity (relative fluorescence), and cellularity (propidium iodide stain). The mice were perfused with formalin and the left eye removed for histopathology. Results: Female mice demonstrated significantly larger CNV than age-matched males (1.6 0.2 DA in females v 1.20.1 DA in males, p<0.05), with similar magnitude of increased vascularity and cellularity. Surprisingly, ovariectomy seemed to decrease CNV size and severity (1.30.1 DA), whereas estrogen supplementation seemed to increase size and severity (2.00.1 DA). Histopathology confirmed that CNV in the estrogen supplementation group in females were larger, thicker and more cellular than in the sham-operated or ovariectomy groups. Estrogen supplementation had no impact on CNV severity in males. Conclusions: Female mice develop more severe CNV than do males. However, estrogen presence seems to increase severity and loss seems to diminish severity, contradictory to the inference drawn from clinical observations. The putative beneficial or detrimental role of estrogen biology in AMD must be more carefully evaluated and may vary with the stage of AMD (atrophic or neovascular) as well as with the specific target cell type (RPE or endothelium).
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