Protection of the Retina by Rapid Diffusion of Hydrogen: Administration of Hydrogen-Loaded Eye Drops in Retinal Ischemia–Reperfusion Injury

Abstract

PURPOSE. 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 (H2) 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 H2-loaded eye drops on retinal I/R injury. METHODS. Retinal ischemia was induced in rats by raising IOP for 60 minutes. H2-loaded eye drops were prepared by dissolv- ing H2 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-deox- yguanosine. Seven days after I/R injury, retinal damage was quantified by measuring the thickness of the retina. RESULTS. When H2-loaded eye drops were continuously admin- istered, H2 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 Mu¨ller glia, astrocytes, and micro- glia. The drops improved the recovery of retinal thickness by 70%. CONCLUSIONS. H2 has no known toxic effects on the human body. Thus, the results suggest that H2-loaded eye drops are a highly useful neuroprotective and antioxidative therapeutic treatment for acute retinal I/R injury. (Invest Ophthalmol Vis Sci. 2010;51:487–492) DOI:10.1167/iovs.09-4089

Study details

Article type

Original Research

Disease / injury model

Retinal ischemia-reperfusion injury (model for acute angle-closure glaucoma, retinal artery occlusion, amaurosis fugax)

Duration

7 days

Dose comparison

H2-loaded eye drops were tested at 25%, 50%, 75%, and 100% concentrations, showing a dose-dependent suppression of retinal thinning. Even 25% H2-loaded drops were effective.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Continuous administration of H2-loaded eye drops in a rat model of retinal ischemia-reperfusion injury rapidly increased H2 concentration in the vitreous body, reduced hydroxyl radical accumulation, decreased apoptotic and oxidative stress marker–positive cells, and prevented retinal thinning. The protective effect was dose-dependent and required H2 presence at the onset of reperfusion. H2-loaded eye drops improved recovery of retinal thickness by approximately 70% and reduced glial activation, suggesting a strong neuroprotective and antioxidative effect.