Hasegawa Tomoko, Ikeda Hanako Ohashi, Iwai Sachiko, Muraoka Yuki, Tsuruyama Tatsuaki, Okamoto-Furuta Keiko, Kohda Haruyasu, Kakizuka Akira, Yoshimura Nagahisa
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
Heliyon. 2018 Mar 1;4(2):e00544. doi: 10.1016/j.heliyon.2018.e00544. eCollection 2018 Feb.
Retinal neuronal cell death underlies many incurable eye diseases such as retinitis pigmentosa (RP) and glaucoma, and causes adult blindness. We have shown that maintenance of ATP levels via inhibiting ATP consumption is a promising strategy for preventing neuronal cell death. Here, we show that branched chain amino acids (BCAAs) are able to increase ATP production by enhancing glycolysis. In cell culture, supplementation of the culture media with BCAAs, but not glucose alone, enhanced cellular ATP levels, which was canceled by a glycolysis inhibitor. Administration of BCAAs to RP mouse models, and , significantly attenuated photoreceptor cell death morphologically and functionally, even when administration was started at later stages. Administration of BCAAs in a glaucoma mouse model also showed significant attenuation of retinal ganglion cell death. These results suggest that administration of BCAAs could contribute to a comprehensive therapeutic strategy for retinal neurodegenerative diseases such as RP and glaucoma.
视网膜神经元细胞死亡是许多无法治愈的眼部疾病（如色素性视网膜炎（RP）和青光眼）的根本原因，并导致成年人失明。我们已经表明，通过抑制ATP消耗来维持ATP水平是预防神经元细胞死亡的一种有前景的策略。在这里，我们表明支链氨基酸（BCAAs）能够通过增强糖酵解来增加ATP的产生。在细胞培养中，向培养基中添加BCAAs而不是单独添加葡萄糖可提高细胞内ATP水平，这一作用可被糖酵解抑制剂消除。向RP小鼠模型给药BCAAs，即使在后期开始给药，在形态和功能上也能显著减轻光感受器细胞死亡。在青光眼小鼠模型中给予BCAAs也显示出视网膜神经节细胞死亡显著减轻。这些结果表明，给予BCAAs可能有助于制定针对RP和青光眼等视网膜神经退行性疾病的综合治疗策略。
