Drug Design, Development and Therapy (Sep 2018)
17β-estradiol ameliorates oxidative stress and blue light-emitting diode-induced retinal degeneration by decreasing apoptosis and enhancing autophagy
Abstract
Qingquan Wei,1,* Xiuwei Liang,2,* Ye Peng,3,* Donghui Yu,1 Ruiling Zhang,1 Huizi Jin,1 Jiaqi Fan,1 Wenting Cai,1 Chengda Ren,1 Jing Yu1,4 1Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 2Department of Ophthalmology, Nanchang University, Nanchang, People’s Republic of China; 3Department of Clinical Laboratory, Shanghai Tenth People’s Hospital Affiliated with Tongji University, Shanghai, People’s Republic of China; 4Department of Ophthalmology, Ninghai First Hospital, Zhejiang, People’s Republic of China *These authors contributed equally to this work Purpose: This study aimed to assess the effects of 17β-estradiol (βE2) on blue light-emitting diode (LED)-induced retinal degeneration (RD) in rats and hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell injury in humans and elucidate the protective mechanism of βE2 underlying these processes.Methods: Female ovariectomized (OVX) rats were intravitreally injected with βE2 before blue LED exposure (3,000 lux, 2 hours). Retinal function and morphology were assayed via electroretinogram (ERG) and H&E, respectively. Cell viability was assayed using the Cell Counting Kit-8. Cell ROS were measured using dichlorofluorescein fluorescence. Apoptosis was evaluated by TUNEL and Annexin V/propidium iodide staining. Gene expression and protein expression were quantified using quantitative real-time RT-PCR, Western blotting, and immunohistochemistry. Autophagosomes were examined by electron microscopy.Results: Female OVX rats were exposed to blue LED, inducing RD. βE2 significantly prevented the reduction in the a- and b-wave ERG amplitudes and the disruption of retinal structure, the loss of photoreceptor cells, and the decrease in the thickness of the outer nuclear layer caused by blue LED exposure. βE2 also decreased cell apoptosis in the retina in blue LED-induced RD. Additionally, βE2 reduced ROS levels and apoptosis in H2O2-treated human retinal pigment epithelial (ARPE-19) cells. Furthermore, βE2 increased the protein expression of p-Akt and Bcl-2 and decreased the protein expression of cleaved caspase-3 and Bax during blue LED-induced retinal damage and in H2O2-treated ARPE-19 cells. βE2 also increased the number of autophagosomes and upregulated the expression of LC3-II/LC3-I and Beclin 1 in these processes.Conclusion: βE2 protects against blue LED-induced RD and H2O2-induced oxidative stress by acting as an antioxidant, and its protective mechanism might occur by reducing apoptosis and enhancing autophagy; βE2 may be a novel and effective therapy for age-related macular degeneration. Keywords: 17β-estradiol, hydrogen peroxide, retinal blue light-emitting diode degeneration, oxidative stress, apoptosis, autophagy
