Neuroprotective effect of inosine on axotomized retinal ganglion cells in adult rats

PURPOSE: To explore the potential survival-promoting effect of inosine on axotomized retinal ganglion cells (RGCs) of adult rats in vivo. METHODS: The left optic nerves (ON) in the subject rats were transected at 1.5 mm from the optic disc. Repeated intraperitoneal injections or single intraocular injection of inosine were administered. The RGCs were retrogradely labeled with a gold fluorescent dye and the density of surviving RGCs in number per square millimeter of retina was calculated in wholemounted retinas. The functional integrity of the blood-retinal barrier (BRB) after ON transection was evaluated with an intravenous injection of Evans blue. RESULTS: In control animals, the mean density of surviving RGCs (number per square millimeter) of the whole retina was 2007 +/- 68 at 2 days (taken as the normal value), 927 +/- 156 at 7 days, and 384 +/- 33 at 14 days after surgery. Repeated intraperitoneal injections (75 mg/kg for each injection) of inosine significantly enhanced RGC survival at 14 days after ON transection (500 +/- 38), whereas no significant difference in the densities was detected at 7 days (974 +/- 101), even when the dosage of inosine was doubled (1039 +/- 61). At this time point, however, a single intraocular injection of inosine significantly increased the density of surviving RGCs (1184 +/- 156). Moreover, more RGCs around the optic disc were rescued when inosine, administered either intraperitoneally or intraocularly, showed a beneficial effect on RGC survival. No breakdown of the BRB after ON transection was detected with the method used in the study. CONCLUSIONS: These findings demonstrate that inosine could protect axotomized RGCs in vivo after ON transection.