Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 52, Issue 5, Pages 909-915Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.12.013
Keywords
Superoxide dismutase; Retinal ganglion cell; Ischemia; Reactive oxygen species; Free radicals
Funding
- National Natural Science Foundation of China [30973260]
- Central South University [2010QZZD026]
- Hunan National Natural Science Foundation [07JJ3041]
- New Century Excellent Talents in University [NCET-10-0829]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
- Key Teacher of Hunan Province
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Retinal ischemia/reperfusion (I/R) results in neuronal death and generation of reactive oxygen species. The aim of this study was to investigate the neuroprotective effect of manganese superoxide dismutase (SOD2) on retinal ganglion cells (RGCs) in an I/R-induced retinal injury model. One eye of each Wistar rat was pretreated with recombinant adeno-associated virus containing the SOD2 gene (MV-SOD2) or recombinant AAV containing the GFP gene (AAV-GFP) by intravitreal injection 21 days before initiation of I/R injury. Retinal I/R injury was induced by elevating intraocular pressure for 1 h, and reperfusion was established immediately afterward. The number of RGCs and the inner plexiform layer (IPL) thickness were measured by Fluorogold retrograde labeling and hematoxylin and eosin staining at 6 h, 24 h, 72 h, and 5 days after injury. Superoxide anion, the number of RGCs, IPL thickness, malondialdehyde (MDA) level, 8-hydroxy-2-deoxyguanosine (8-OHdG) level, MnSOD (manganese superoxide dismutase) activity, and nitrotyrosine level were measured by fluorescence staining, immunohistochemistry, and enzyme-linked immunosorbent analysis at 5 days after I/R injury. Severe RGC loss, reduced IPL thickness, reduced MnSOD activity, and increased superoxide ion, MDA, 8-OHdG, and nitrotyrosine production were observed after I/R injury. Administration of AAV-SOD2 significantly reduced the levels of superoxide ion, MDA, 8-OHdG, and nitrotyrosine and prevented the damage to RGCs and IPL Delivery of the antioxidant gene inhibited I/R-induced RGC and IPL damage by reducing oxidative stress and nitrative stress, suggesting that MnSOD may be relevant for the neuroprotection of the inner retina from I/R-related diseases. (C) 2011 Elsevier Inc. All rights reserved.
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