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Takahiko Noro, Kazuhiko Namekata, Yuriko Azuchi, Atsuko Kimura, Xiaoli Guo, Chikako Harada, Tadashi Nakano, Hiroshi Tsuneoka, Takayuki Harada; Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(8):5012-5019. doi: 10.1167/iovs.15-17142.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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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