Contribution to ischemic injury of rat optic nerves by intracellular sodium overload.

Abstract

Ischemic insult to axons of retinal ganglion cells (RGCs) is believed to contribute significantly to preferential loss of RGCs in glaucoma. In this study, we characterized the role of intracellular Na(+) overload in ischemic injury of acutely isolated rat optic nerves by evaluating electrically elicited compound action potentials (CAPs) from the optic nerves. Under control conditions, robust and stable CAPs can be recorded for more than 5 h. One hour of oxygen and glucose deprivation (OGD) that simulates ischemia, virtually eliminated the CAP. Upon returning to control conditions, the CAP gradually recovered. Maximum recovery (35% of control) was obtained by 1 h after returning to normal oxygenated Ringer. When a rapidly reversible Na(+) channel blocker, that completely blocked the CAP under control conditions, was present during OGD, the recovery of the CAP was significantly enhanced to 65% of control. When the Na(+) was replaced with either choline or Li(+) in the Ringer during OGD, CAP recovery was significantly enhanced (65-70% of control). Removing Ca(++) from the Ringer (plus 5 mM EGTA) provided even better preservation of the CAP following OGD (90% of control). Our results are consistent with the hypothesis that intracellular Na(+) overload appears to play a significant role in ischemic injury of optic nerves. This Na(+) overload may depend at least partially upon Ca(++) influx from the extracellular space.