Abstract
Abstract: :
Purpose:To evaluate the neuroprotective effect of AD4 on the survival of retinal ganglion cells (RGCs), in an established model of experimental glaucoma in rats. AD4 is a new antioxidant compound which crosses blood brain barrier, and it has neuroprotective effect in animal model of multiple sclerosis. The neuroprotective effect of AD4 is associated with the inhibition of matrix metalloproteinases production. Methods: Glaucoma was induced in one eye of 32 Wistar rats by using the translimbal laser photocoagulation model. Twenty rats were randomized one week before the first laser treatment to get intraperitoneal injections of either AD4 6/mg/kg/day or saline. Another group of twelve rats were randomized by the same manner, but the dosage of AD4 was 330mg/kg/day .Second laser treatment was done one week after the first laser. Four weeks after initial laser treatment, retinal ganglion cells were labeled by applying fluorescent dye (Rhodamine Dextran) to the optic nerve. Labeling was done by transecting the optic nerves and applying the dye to the cut end of the nerve. 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. Survival of RGCs was compared between treatment group and control using student t– test. Results:IOP was elevated in all rats after the laser treatment. The rise of IOP in the AD4 treated groups was similar to the rise of IOP in the saline treated groups. The mean number of surviving RGCs was not significantly different in the AD4 treated groups (in both dosages), compared to the saline control groups. After 4 weeks of glaucoma the number of surviving RGCs was 2579+1206 cells (n=4) in the AD4 6/mg/kg/day group compared to 2735+1080 cells (n=6) in the control group (t test, p=0.846). The number of surviving RGCs in the AD4 330/mg/kg/day group was 4338+546cells (n=5) compared to 4632+432cells in the control group(n=4), (t test, p=0.411). No neuroprotective effect of AD4 was demonstrated in either dosage. Conclusion: Our results show that intraperitoneal injections of the antioxidant compound AD4 have no impact on the survival of RGCs in rats with experimental glaucoma.
Keywords: neuroprotection • retina: proximal (bipolar, amacrine, and ganglion cells) • neuroprotection