Minocycline is Neuroprotective in a Rat Model of Optic Nerve Transection

Abstract

Abstract: : Purpose: To evaluate the neuroprotective effect of Minocycline on the survival of retinal ganglion cells (RGCs) after optic nerve transection in rats. Minocycline is an antimicrobial and anti-inflammatory common drug used orally by humans. Recently, it was shown that it has remarkable neuroprotective qualities in animal models of cerebral ischemia, traumatic brain injury, and Huntington's and Parkinson's disease. The neuroprotective effect of Minocycline is associated with marked inhibition of NO synthase, caspase family expression, and p38 (MAPK). Methods: Twenty eight Wistar rats were divided into 2 groups. One group was treated by daily intraperitoneal injections of saline and the other by daily intraperitoneal injections of Minocycline15mg/Kg-20mg/Kg. Three days after the beginning of treatment optic nerve transection was performed unilaterally 3-4mm behind the globe. One week later Rhodamine Dextran was applied to the orbital optic nerve, 1-2 mm behind the globe, in order to label the RGCs. A day later eyes were enucleated and retinas were prepared as whole mounts. Using Fluorescence microscope, labeled RGCs were counted by an observer masked to the experimental protocol. Results: One week after optic nerve transection the mean number of surviving RGCs was significantly higher in the Minocycline treated group (n=13, 2097 + 538 cells) compared to the saline treated group (n=11, 1499 + 589 cells) (t test, p=0.01). Four rats died. The neuroprotective effect of Minocycline was more pronounced in the peripheral zone of the retina. Conclusions: Our results suggest that intraperitoneal injections of Minocycline significantly enhance the survival of RGCs after optic nerve transection in rats.

Keywords: neuroprotection • ganglion cells