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.


CONCLUSIONS
Minocycline significantly enhances the survival of RGCs after ONT and in experimental glaucoma by delaying the apoptosis pathway.


CONCLUSIONS
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.
Levkovitch-Verbin
Hani
H
Sam Rothberg Ophthalmic Molecular Biology Laboratory, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel. halevko@hotmail.com
Kalev-Landoy
Maia
M
Habot-Wilner
Zohar
Z
Melamed
Shlomo
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D007274:Injections, Intraperitoneal; D008911:Minocycline / Q000008:administration & dosage / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
D018696:Neuroprotective Agents; D008911:Minocycline