Minocycline delays death of retinal ganglion cells in experimental glaucoma and after optic nerve transection

Objective: To evaluate the effect of minocycline hydrochloride on the survival of retinal ganglion cells (RGCs) in glaucomatous rat eyes and rat eyes after optic nerve transection (ONT). Methods: The effect of intraperitoneal injections of minocycline at dosages of 15 mg/kg per day, 22 mg/kg per day, and 45 mg/ kg per day was evaluated and compared with saline in ONT (n=174) and experimental glaucoma (n=51). Results: The mean +/- SEM survival rate of RGCs 1 week after ONT was significantly higher with minocycline at dosages of 15 mg/ kg per day (36% +/- 3%; n=9; P=.04), 22 mg/ kg per day (44% +/- 2%; n=15; P=.001), and 45 mg/ kg per day (39% +/- 3%; n=10; P=.008) compared with saline (29% +/- 2%; n=28). Minocycline at a dosage of 22 mg/ kg per day was also significantly neuroprotective compared with saline 2 weeks after ONT (mean +/- SEM survival rate, 5% +/- 1% vs 3% +/- 0.4%, respectively; n=20 [10 rats in each group]; P=.03). In experimental glaucoma, the mean +/- SEM percentage of RGCs after 4 weeks was 84% +/- 4% in the minocycline group (n=15) compared with 65% +/- 4% in the saline group (n=18) (P=.003). Apoptosis of RGCs was significantly delayed by minocycline 4 days and 1 week after ONT. Conclusion: Minocycline significantly enhances the survival of RGCs after ONT and in experimental glaucoma by delaying the apoptosis pathway. Clinical Relevance: The safety record of minocycline and its ability to penetrate the blood-brain barrier suggest that this drug is a promising neuroprotective drug for optic nerve injuries.