NADPH-diaphorase reactive neurons of the rabbit retina: differential sensitivity to excitotoxins and unusual morphologic features.

Various populations of retinal and brain neurons display different degrees of sensitivity to the toxic effects of excitatory amino acid agonists. To further define this phenomenon, the effects of intravitreal injections of kainic acid, N-methyl-D-aspartate (NMDA), quinolinic acid, and ibotenic acid on NADPH-diaphorase (NADPHd) reactive cells of the rabbit retina were examined. In normal rabbit retinas, NADPHd histochemistry selectively stains two populations of cells at the inner margin of the inner plexiform layer: large densely staining (Type I) and more numerous, smaller and lightly staining (Type II) cells. All of the toxins studied destroy both cell types at high doses. Kainic acid, however, at low doses destroys Type I cells but selectively spares Type II cells. NMDA injections result in a more complex and less consistent pattern of cell loss; overall, the Type I cells are perhaps slightly resistant to this agent as compared to Type II cells. The Type I neurons in this respect are analogous to striatal NADPHd-reactive neurons, which have, at most, a slight relative resistance to NMDA neurotoxicity. The excitotoxin lesions reduce the complexity of the fiber plexus in the inner plexiform layer and thereby reveal anatomic features of surviving NADPHd reactive neurons that are not apparent in normal retinas. In particular, each Type I cell gives off several fine, straight, beaded processes that emanate from dendrites and run several millimeters in the inner plexiform layer. These processes are presumably involved in long-distance interactions within the retina. Excitotoxin lesions may provide a generally useful anatomic tool for elucidating morphological features of neurons stained by histochemical and immunohistochemical methods.