Estrogen Ameliorates Photoreceptor Cell Loss In Light-Induced Retinal Degenerated Balb/C Mice

Purpose: Estrogen or 17β-estradiol (17β-E2) is known to act as an antioxidant and has neuroprotective effects. 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. Methods: 3-5 months old Balb/c mice were exposed to constant light of ~1500 lux. Mice were divided into four groups and treated via intraperitoneal injections with vehicle, 17β-E2, the ER β inhibitor [4-(2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl)phenol, (PHTPP), or a combination of 17β-E2 and PHTPP. Retinal function was evaluated by electroretinogram (ERG), and eyes were assessed by histology and immunohistochemistry. Results: Light damage resulted in a loss of the number of photoreceptor nuclei in the outer nuclear layer (ONL), a loss of UV cone opsin immunoreactivity and a reduction in rod- and cone-mediated ERG signals. 17β-E2 treatment significantly increased the ONL cell count and increased the rod-driven a-wave in the ERG. PHTPP alone had no effect, but PHTPP eliminated the protective effect of exogenously applied estrogen. Likewise, 17β-E2 significantly increased the amount of UV cone opsin immunoreactivity, an effect that was negated by co-administration of PHTPP. Conclusions: Estrogen supplementation was found to reduce rod and cone photoreceptor cell damage in this light-induced photoreceptor degeneration mouse model, an effect that was mediated via ERβ activation.