The contribution of various NOS gene products to HIV-1 coat protein (gp120)-mediated retinal ganglion cell injury.

ABSTRACT

PURPOSE: There is growing evidence that the neuronal pathology seen with HIV-1 is mediated, at least in part, through an excitotoxic/free radical pathway. Nitric oxide (NO) plays a critical role in the nervous system, in both normal and pathologic states, and appears to be involved in a variety of excitotoxic pathways. Whether isoforms of nitric oxide synthase (NOS) are involved in gp120-mediated neuronal loss in the retina was therefore explored. METHODS: To determine which (if any) of the various isoforms of NOS are critical in gp120-mediated damage in the retina, neuronal NOS-deficient [nNOS(-/-)], endothelial NOS-deficient [eNOS(-/ -)], and immunologic NOS-deficient [iNOS(-/-)] mice were subjected to intravitreal injections of gp120. RESULTS: Retinal ganglion cells in the nNOS(-/-) mouse were relatively resistant to gp120, manifesting attenuation of gp120-induced injury compared with wild-type mice. The iNOS(-/-) and eNOS(-/-) mice were as susceptible to gp120 toxicity as control animals. NOS inhibitors were protective against this toxicity. CONCLUSIONS: The presence of nNOS is a prerequisite for the full expression of gp120-mediated loss in the retina; eNOS and iNOS do not appear to play a significant role.