Evaluation of potential topical and systemic neuroprotective agents for ocular hypertension-induced retinal ischemia-reperfusion injury

Objective To evaluate for drugs with superior neuroprotective efficacy and investigate their underlying mechanisms related to antioxidation. Procedures Brinzolamide (1%), timolol (0.5%), minocycline (22 mg./kg), lidocaine (1.5 mg./kg), and methylprednisolone (30 mg./kg) were administered to Sprague-Dawley (SD) rats. The retina was evaluated by electroretinography and histological analysis. The antioxidative capacity of drugs was evaluated to clarify the underlying mechanism. The oxidant/antioxidant profiles of plasma, red blood cells, and retina were analyzed by lipid peroxidation (malondialdehyde) and by measuring the activities of antioxidants. Proteomic analysis was used to investigate the possible protective mechanisms of the drug against ischemia-reperfusion injury. Results The results suggested that timolol, methylprednisolone, and minocycline protected retinal function. Methylprednisolone and minocycline possessed good antioxidative activity. Brinzolamide and lidocaine preserved the structural integrity of the retina, but not retinal function. Conclusion Methylprednisolone, minocycline, and timolol have potential acute or delayed benefit in retinal ischemia-reperfusion injury. Their neuroprotective actions depend at least partially on the ability to alleviate oxidative stress.