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Mausumi Bandyopadhyay, Elizabeth O'Quinn, Lara Seidman, Baerbel Rohrer; Estrogen Reduces Photoreceptor Cell Loss In A Light-induced Photoreceptor Degeneration Mouse Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2572.
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Females are more susceptible to age related macular degeneration than males. The purpose of this study is to evaluate the effects of estrogen and estrogen receptor beta (ERβ) on photoreceptor cell structure and function in an experimental model for light-induced photoreceptor degeneration, the light damage mouse model.
3-5 months old Balb/c mice were exposed to constant light of ~150 lux. Mice were divided into four groups and treated via IP injections. The first group received 0.2 mg/kg body weight 17β-estradiol each day for 10 days, the second group received 25 µg/kg body weight ERβ inhibitor [4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl)phenol, PHTPP] every alternate day; the third group received combination of 17β-estradiol and PHTPP and the fourth group received vehicle. Rod cell function was assessed using electroretinogram (ERG) recordings in dark-adapted animals. Optokinetic Response (OKR) measurements were used to assess cone photoreceptor function. Tissues were collected for histological and biochemical studies.
Rod photoreceptor survival was assessed by ERG and by determining rows of photoreceptor in the outer nuclear layer (ONL). Our results showed that, estrogen treatment significantly (P<0.001) increased rows of photoreceptor in ONL than vehicle treated control; whereas the ERβ inhibitor treatment reduced (P<0.001) photoreceptor cell numbers. Co-administering PHTPP and estrogen eliminated the protective effect of estrogen. ERG analysis showed good correlation between protection of structure and function; the rod photoreceptor-driven a- wave response was increased in the estrogen treated group, while ERβ inhibitor treated group showed a significant decrease (P<0.01) when compared to the control mice. Likewise, estrogen treatment was found to increase cone cell function (P<0.01) as demonstrated by OKR analysis; and immunohistochemistry indicated lower cone opsin level in the ERβ inhibitor, combination and vehicle treated mice whereas estrogen treatment has been found to improve cone opsin protein level.
We found that estrogen treatment reduced photoreceptor cell damage in this light-induced photoreceptor degeneration mouse model. The estrogen receptor inhibitor experiments suggest that the protective effect is mediated via ERβ.
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