Lidocaine toxicity to rat retinal ganglion cells

Purpose. To examine the effects of the local anesthetic, lidocaine, on rat retinal ganglion cells (RGC) in vitro and in a modified in vivo assay. Methods. For in vitro experiments, RGC were dissociated from freshly harves ted Long Evan's rat pup retinas. The RGC were incubated overnight with vary ing concentrations of lidocaine (0.5-12.0 mM). Surviving cells were assayed at 24 hours. In an ill vivo assay, 7-day-old Long-Evans rat pups were anes thetized and 2 mu l of lidocaine (final intraocular concentration: 0.03-15 mM) or vehicle was injected intravitreally. Intravitreal coinjection of nim odipine or MK801 (dizocilpine) were also performed in a subset of animals. A week after injection, rat pups were sacrificed and each retina removed, d issociated and plated separately. RGC survival was immediately assessed. Li ving RGC were identified on the basis of morphology and counted in a masked fashion. Results. Lidocaine is toxic in a dose dependent fashion to RGC in vitro. Lo wer concentrations (0.5 mM and 1.0 mM) were non-toxic; 2.0, 6.0 and 12.0 mM lidocaine killed 25%, 88% and 99% of the RGC respectively. Intravitreal li docaine was also toxic to RGC in a dose dependent fashion. Lidocaine concen trations of 3.0 mM, 7.5 mM and 15 mM killed 25%, 38% and 44% of the RGC. Th is effect was blocked by the simultaneous administration of either nimodipi ne or MK801. Conclusions. Lidocaine is toxic to RGC both in vitro and in vivo. This effe ct is blocked in vivo by the simultaneous administration of agents known to block glutamate mediated neuronal death, suggesting that excitotoxicity ma y be involved in this process.