Hamilton Glaucoma Center, Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA.
Hamilton Glaucoma Center, Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2639-2645. doi: 10.1016/j.bbrc.2018.08.016. Epub 2018 Aug 11.
Coenzyme Q10 (CoQ) protects retinal ganglion cells (RGCs) in experimental retinal ischemia and glaucoma by scavenging reactive oxygen species. We tested whether a diet supplemented with ubiquinol, the reduced form of CoQ, promotes RGC survival and blocks the apoptotic pathway in ischemic mouse retina induced by acute high intraocular pressure (IOP) elevation. Ubiquinol (1%) treatment significantly promoted RGC survival at 2 weeks after ischemia/reperfusion. The ubiquinol treatment significantly blocked activation of astroglial and microglial cells in the ischemic retina at 2 weeks. While the ubiquinol treatment significantly decreased active Bax protein expression in the ischemic retina, phosphorylation of Bad at serine 112 and Bcl-xL protein expression were preserved in the ubiquinol-treated ischemic retina at 12 h. Consistently, the ubiquinol treatment prevented apoptotic cell death by blocking caspase-3 cleavage. These results suggest that the ubiquinol enhances RGC survival by modulating the Bax/Bad/Bcl-xL-mediated apoptotic pathway in the ischemic retina. Ubiquinol has therapeutic potential for ameliorating elevated IOP-induced ischemic retinal degeneration.
辅酶 Q10 (CoQ) 通过清除活性氧来保护实验性视网膜缺血和青光眼的视网膜神经节细胞 (RGC)。我们测试了富含还原型 CoQ 的泛醇（ ubiquinol）饮食是否能促进 RGC 存活并阻断急性高眼压 (IOP) 升高引起的缺血性鼠视网膜中的细胞凋亡途径。泛醇 (1%) 处理在缺血/再灌注后 2 周内显著促进了 RGC 的存活。泛醇处理在 2 周时显著阻断了缺血视网膜中星形胶质细胞和小胶质细胞的激活。虽然泛醇处理在缺血视网膜中显著降低了活性 Bax 蛋白的表达，但在 12 小时时，缺血视网膜中 Bad 蛋白在丝氨酸 112 位点的磷酸化和 Bcl-xL 蛋白的表达得以保留。一致地，泛醇处理通过阻断半胱氨酸天冬氨酸蛋白酶-3 的裂解来阻止细胞凋亡。这些结果表明，泛醇通过调节缺血视网膜中 Bax/Bad/Bcl-xL 介导的细胞凋亡途径来增强 RGC 的存活。泛醇具有改善升高的 IOP 诱导的缺血性视网膜变性的治疗潜力。
