Journal of Molecular Neuroscience

, Volume 55, Issue 1, pp 141–151 | Cite as

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

  • Shaolan Wang
  • Baoying Wang
  • Yan Feng
  • Mingshu Mo
  • Fangying Du
  • Hongbo Li
  • Xiaorui Yu
Article
First Online:
Received:
Accepted:

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.

Keywords

Neuroprotection 17β-estradiol Retinal light damage Oxidative stress Intravitreal injection Antioxidation 

Abbreviations

βE2

17β-estradiol

LD

Light damage

IVI

Intravitreal injection

OVX

Ovariectomized

AMD

Age-related macular degeneration

ERG

Electroretinogram

MDA

Malondialdehyde

CAT

Catalase

Gpx

Glutathione peroxidase

SOD

Superoxide dismutase

Trx

Thioredoxin

Nrf2

Nuclear factor erythroid 2-related factor 2

HO-1

Heme oxygenase-1

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Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 30672286 and no. 81271013) and the National Research Foundation for the Doctoral Program of Higher Education of China (no. 20120201110051).

Conflict of Interest

None.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shaolan Wang
    • 1
  • Baoying Wang
    • 1
  • Yan Feng
    • 1
  • Mingshu Mo
    • 1
  • Fangying Du
    • 1
  • Hongbo Li
    • 1
  • Xiaorui Yu
    • 1
    • 2
  1. 1.Department of Genetics and Molecular Biology, School of MedicineXi’an Jiaotong UniversityXi’anChina
  2. 2.Key Laboratory of Environment- and Gene-Related Diseases of the Ministry of Education, School of MedicineXi’an Jiaotong UniversityXi’anChina

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