Department of Ophthalmology, Musashikosugi Hospital, Nippon Medical School, Kanagawa, Japan.
Invest Ophthalmol Vis Sci. 2010 Jan;51(1):487-92. doi: 10.1167/iovs.09-4089. Epub 2009 Oct 15.
Retinal ischemia-reperfusion (I/R) injury by transient elevation of intraocular pressure (IOP) is known to induce neuronal damage through the generation of reactive oxygen species. Study results have indicated that molecular hydrogen (H(2)) is an efficient antioxidant gas that selectively reduces the hydroxyl radical (*OH) and suppresses oxidative stress-induced injury in several organs. This study was conducted to explore the neuroprotective effect of H(2)-loaded eye drops on retinal I/R injury.
Retinal ischemia was induced in rats by raising IOP for 60 minutes. H(2)-loaded eye drops were prepared by dissolving H(2) gas into a saline to saturated level and administered to the ocular surface continuously during the ischemia and/or reperfusion periods. One day after I/R injury, apoptotic cells in the retina were quantified, and oxidative stress was evaluated by markers such as 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine. Seven days after I/R injury, retinal damage was quantified by measuring the thickness of the retina.
When H(2)-loaded eye drops were continuously administered, H(2) concentration in the vitreous body immediately increased and I/R-induced *OH level decreased. The drops reduced the number of retinal apoptotic and oxidative stress marker-positive cells and prevented retinal thinning with an accompanying activation of Müller glia, astrocytes, and microglia. The drops improved the recovery of retinal thickness by >70%.
H(2) has no known toxic effects on the human body. Thus, the results suggest that H(2)-loaded eye drops are a highly useful neuroprotective and antioxidative therapeutic treatment for acute retinal I/R injury.
已知通过短暂升高眼内压（IOP）引起的视网膜缺血再灌注（I/R）损伤会通过产生活性氧物种引起神经元损伤。研究结果表明，分子氢（H2）是一种有效的抗氧化气体，它选择性地减少羟基自由基（*OH），并抑制几种器官中氧化应激诱导的损伤。本研究旨在探讨负载氢气滴眼剂对视网膜 I/R 损伤的神经保护作用。
通过将 IOP 升高 60 分钟来诱导大鼠视网膜缺血。将 H2 气体溶解在生理盐水中至饱和水平，制备负载 H2 的滴眼剂，并在缺血和/或再灌注期间连续施用于眼表面。在 I/R 损伤后 1 天，定量视网膜中的凋亡细胞，并通过 4-羟基壬烯醛和 8-羟基-2-脱氧鸟苷等标志物评估氧化应激。在 I/R 损伤后 7 天，通过测量视网膜的厚度来定量视网膜损伤。
当连续给予负载 H2 的滴眼剂时，玻璃体中的 H2 浓度立即增加，I/R 诱导的*OH 水平降低。滴眼剂减少了视网膜凋亡和氧化应激标志物阳性细胞的数量，并防止了视网膜变薄，同时激活了 Müller 胶质细胞、星形胶质细胞和小胶质细胞。滴眼剂使视网膜厚度的恢复超过 70%。
H2 对人体没有已知的毒性作用。因此，结果表明负载 H2 的滴眼剂是治疗急性视网膜 I/R 损伤的一种非常有用的神经保护和抗氧化治疗方法。
