THE ROLE OF NEURONAL AND ENDOTHELIAL NITRIC-OXIDE SYNTHASE IN RETINALEXCITOTOXICITY

Purpose. Nitric oxide synthase (NOS) plays an essential role in neuron al function and is critical in the brain for normal and pathologic res ponses to glutamate. The role of NOS in the retina is less well unders tood. The retina provides an experimental system in which the intrinsi c circuitry is well defined: retinal excitotoxic damage has been well characterized. Methods. To determine whether neuronal NOS (nNOS) and e ndothelial NOS (eNOS) are critical in excitotoxic damage in the retina , nNOS- and eNOS-deficient mice were subjected to intravitreal injecti ons of N-methyl-D-aspartate (NMDA) or to arterial occlusions. Results. Retinal ganglion cells in the nNOS-deficient mouse were relatively re sistant to NMDA and to arterial occlusion. In contrast, the damage in the eNOS-deficient mouse retina was not distinguishable from that in c ontrol animals. Preinjection with an NOS inhibitor was partially prote ctive. Conclusions. The presence of nNOS is a prerequisite for the ful l expression of excitotoxicity in the retina; eNOS does not appear to play a significant role.