Takahiko Noro1, Kazuhiko Namekata2, Yuriko Azuchi2, Atsuko Kimura2, Xiaoli Guo2, Chikako Harada2, Tadashi Nakano3, Hiroshi Tsuneoka3, Takayuki Harada2. 1. Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan 2Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan. 2. Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 3. Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
Abstract
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.
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.
Authors: Kanchan Phadwal; Dominic Kurian; Muhammad Khalid F Salamat; Vicky E MacRae; Abigail B Diack; Jean C Manson Journal: Sci Rep Date: 2018-07-03 Impact factor: 4.379