NADPH diaphorase activity in the rabbit retina is modulated by glutamatergic pathways

NADPH diaphorase activity in the rabbit retina is modulated by the state of visual adaptation. In this study, we tested possible glutamatergic control of this phenomenon. Rabbits were injected intravitreally with agonists and antagonists of glutamate. After adaptation (3 hours) to either room light or darkness, the rabbits were killed and the retinae were prepared for NADP H diaphorase histochemistry. Kainic acid significantly reduced the number o f NADPH diaphorase amacrine cells but augmented NADPH diaphorase activity i n horizontal cells in both light- and dark-adapted animals. 6,7-Dinitroquin oxaline-2,3(1H,4H)dione exerted no effect on amacrine cells but eliminated NADPH diaphorase activity in horizontal cells. 2-Amino-4-phosphono butyric acid did not affect NADPH diaphorase activity in horizontal cells but reduc ed the degree of staining in the neuronal processes of amacrine cells. MK-8 01 and N-methyl-D-aspartic acid (NMDA) had no effect on NADPH diaphorase ac tivity in horizontal cells. However, MK-801 reduced staining in the neurona l processes of amacrine cells but not in their cell bodies. NMDA effects we re expressed in a significant reduction in the number and size of amacrine cells that were NADPH diaphorase positive. These results indicate that acti vation of NADPH diaphorase in horizontal cells by darkness is mediated by t he activation of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid (KA)-type glutamate receptors. The ON pathway in the ret ina is probably involved in modulation of NADPH diaphorase in the neuronal processes of amacrine cells. Amacrine cells that are NADPH diaphorase posit ive contain NMDA-type and BMPA/KA-type receptors and are highly susceptible to NMDA and kainic acid toxicity. J. Comp. Neurol. 431: 28-38, 2001. (C) 2 001 Wiley-Liss. Inc.