期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 56, 期 8, 页码 5012-5019出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.15-17142
关键词
spermidine; oxidative stress; neuroprotection; glaucoma; animal model
资金
- Grants-in-Aid for Scientific Research [15H04999, 25430082, 25462766, 26640048] Funding Source: KAKEN
PURPOSE. To assess the therapeutic potential of spermidine in mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma. METHODS. Spermidine, at 30 mM in drinking water, was administered to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, and the measurement of intraocular pressure (IOP) were performed at 5, 8, and 12 weeks old. Histopathology analyses were carried out at 8 and 12 weeks old, and immunoblot and immunohistochemical analyses of 4-hydroxy-2-nonenal (4-HNE) in the retina were performed at 8 weeks old. RESULTS. Spermidine ameliorated retinal degeneration and improved visual function in EAAC1 KO mice at both 8 and 12 weeks old, without affecting IOP. A significant increase of 4-HNE was observed in vehicle-treated EAAC1 KO mice, but spermidine treatment reduced this increase, suggesting that spermidine alleviated the severity of the glaucoma-like phenotype by acting as an antioxidant. CONCLUSIONS. The results from this study suggest that oral spermidine administration could be a useful treatment for retinal degenerative disorders including glaucoma.
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