17β-Estradiol Ameliorates Light-Induced Retinal Damage in Sprague–Dawley Rats by Reducing Oxidative Stress

Abstract

Oxidative stress is considered as a major cause of light-induced retinal neurodegeneration. The protective role of 17β-estradiol (βE2) in neurodegenerative disorders is well known, but its underlying mechanism remains unclear. Here, we utilized a light-induced retinal damage model to explore the mechanism by which βE2 exerts its neuroprotective effect. Adult male and female ovariectomized (OVX) rats were exposed to 8,000 lx white light for 12 h to induce retinal light damage. Electroretinogram (ERG) assays and hematoxylin and eosin (H&E) staining revealed that exposure to light for 12 h resulted in functional damage to the rat retina, histological changes, and retinal neuron loss. However, intravitreal injection (IVI) of βE2 significantly rescued this impaired retinal function in both female and male rats. Based on the level of malondialdehyde (MDA) production (a biomarker of oxidative stress), an increase in retinal oxidative stress followed light exposure, and βE2 administration reduced this light-induced oxidative stress. Quantitative reverse-transcriptase (qRT)-PCR indicated that the messenger RNA (mRNA) levels of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were downregulated in female OVX rats but were upregulated in male rats after light exposure, suggesting a gender difference in the regulation of these antioxidant enzyme genes in response to light. However, βE2 administration restored or enhanced the SOD and Gpx expression levels following light exposure. Although the catalase (CAT) expression level was insensitive to light stimulation, βE2 also increased the CAT gene expression level in both female OVX and male rats. Further examination indicated that the antioxidant proteins thioredoxin (Trx) and nuclear factor erythroid 2-related factor 2 (Nrf2) are also involved in βE2-mediated antioxidation and that the cytoprotective protein heme oxygenase-1 (HO-1) plays a key role in the endogenous defense mechanism against light exposure in a βE2-independent manner. Taken together, we provide evidence that βE2 protects against light-induced retinal damage via its antioxidative effect, and its underlying mechanism involves the regulation of the gene expression levels of antioxidant enzymes (SOD, CAT, and Gpx) and proteins (Trx and Nrf2). Our study provides conceptual evidence in support of estrogen replacement therapy for postmenopausal women to reduce the risk of age-related macular degeneration.

Effects of 17β-estradiol and 2-methoxyestradiol on the oxidative stress-hypoxia inducible factor-1 pathway in hypoxic pulmonary hypertensive rats

“…Determining whether E2 inhibits the expression of HIF-1α by regulating oxidative stress will help to further the understanding of the mechanism of action of E2 in HPH. Wang et al (34) previously revealed that E2 protects against light-induced retinal damage via its antioxidative effect, and the etiology of this involves the upregulation of the gene expression levels of SOD. Liu et al (35) suggested that E2 upregulates SOD2 expression, resulting in reduced ROS generation, which largely favors cardiovascular function.…”

Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats

“…This is particularly important given the ability of E 2 to protect: (i) the heart against trauma-induced myocardial damage in male rats (Hsu et al, 2009), (ii) the developing rat brain against the detrimental effects of ethanol (Ramezani et al, 2011), (iii) against vascular oxidative stress (Ceravolo et al, 2013), and (iv) against retinal oxidative stress in male and female rats (Wang et al, 2014). While our study is the first to show significant enhancement of LV catalase by E 2 in male rats, the additional enhancement of catalase and mitALDH activities in E 2 /ethanol treated rats (Fig.…”

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

“…Our results are supported by findings by Wang and colleagues in Sprague-Dawley rats. They demonstrated a protective effect of 17β-estradiol that increases the retinas own anti-oxidant defenses [37]. Kaja S and colleagues also reported a protective role for estrogen in protecting the inner retina from ischemia-induced damage in rat model [33].…”