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| Oxidative stress is thought to be a major cause of light induced retinal neurodegeneration. The protective role of 17β-estradiol (βE2) in neurodegenerative disorders is well known, however, the underlying mechanism remains unclear. Here, we applied light induced retinal damage model to explore the mechanism by which βE2 exerts its neuroprotection. Adult male and female- ovariectomized (OVX) rats were exposed to 8000 lx white light for 12h to induce retinal light damage. Electroretinogram (ERG) assay and hematoxylin and eosin (H&E) staining show that exposure to light for 12h resulted in functional damage to the rat retina, histological changes and retinal neurons loss, while intravitreal injection (IVI) with βE2 significantly rescued impaired retina function in both female and male rats. By detecting malonylodialdehyde (MDA) production (a biomarker for oxidative stress) indicated an increasing retinal oxidative stress following exposure to light, and βE2 reduced the light induced oxidative stress. qRT-PCR indicated that antioxidant enzymes SOD and Gpx mRNA level were diminished in female-OVX rats but up-regulated in male rats after exposing to light, suggesting a gender differences in regulating the genes of these antioxidant enzymes in response to light. However, administration of βE2 recovered or enhanced the SOD and Gpx expression upon light stimulation. In spite of the CAT expression was not sensitive to light, βE2 also increased the gene expressions both in female-OVX and male rats. Further study indicated the antioxidant proteins Trx and Nrf2 were also involved in βE2 mediated anti-oxidation, while cytoprotective HO-1 exerts a key role in endogenous defense mechanisms against light but not via βE2. Taken together, we provide evidence that βE2 protected the retinal from light damage via anti-oxidative effect, the underline mechanism involved in regulation of the genes of antioxidant enzymes (SOD, CAT, Gpx) and proteins (Trx and Nrf2). Our study will provide the theory evidence for estrogen replacement therapy in postmenopausal women for reducing the risk of Age-related macular degeneration. |
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| Keywords:Neuroprotection, 17β-Estradiol, Retinal light damage, Oxidative stress, Intravitreal injection, Anti-oxidation. |
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