Investigative Ophthalmology & Visual Science, Vol 38, 2038-2044, Copyright © 1997 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

The role of neuronal and endothelial nitric oxide synthase in retinal excitotoxicity

CK Vorwerk, BT Hyman, JW Miller, D Husain, D Zurakowski, PL Huang, MC Fishman and EB Dreyer
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA.

PURPOSE: Nitric oxide synthase (NOS) plays an essential role in neuronal function and is critical in the brain for normal and pathologic responses to glutamate. The role of NOS in the retina is less well understood. The retina provides an experimental system in which the intrinsic circuitry is well defined; retinal excitotoxic damage has been well characterized. METHODS: To determine whether neuronal NOS (nNOS) and endothelial NOS (eNOS) are critical in excitotoxic damage in the retina, nNOS- and eNOS-deficient mice were subjected to intravitreal injections of N-methyl-D-aspartate (NMDA) or to arterial occlusions. RESULTS: Retinal ganglion cells in the nNOS- deficient mouse were relatively resistant to NMDA and to arterial occlusion. In contrast, the damage in the eNOS-deficient mouse retina was not distinguishable from that in control animals. Preinjection with an NOS inhibitor was partially protective. CONCLUSIONS: The presence of nNOS is a prerequisite for the full expression of excitotoxicity in the retina; eNOS does not appear to play a significant role.

This article has been cited by other articles:

				N. Belforte, M. C. Moreno, C. Cymeryng, M. Bordone, M. I. Keller Sarmiento, and R. E. Rosenstein Effect of Ocular Hypertension on Retinal Nitridergic Pathway Activity Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2127 - 2133. [Abstract] [Full Text] [PDF]

				S.-i. Manabe, Z. Gu, and S. A. Lipton Activation of Matrix Metalloproteinase-9 via Neuronal Nitric Oxide Synthase Contributes to NMDA-Induced Retinal Ganglion Cell Death Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4747 - 4753. [Abstract] [Full Text] [PDF]

				K. Takahata, H. Katsuki, T. Kume, D. Nakata, K. Ito, S. Muraoka, F. Yoneda, S. Kashii, Y. Honda, and A. Akaike Retinal Neuronal Death Induced by Intraocular Administration of a Nitric Oxide Donor and Its Rescue by Neurotrophic Factors in Rats Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1760 - 1766. [Abstract] [Full Text] [PDF]

				K. Mizuno, T. Koide, M. Yoshimura, and M. Araie Neuroprotective Effect and Intraocular Penetration of Nipradilol, a {beta}-Blocker with Nitric Oxide Donative Action Invest. Ophthalmol. Vis. Sci., March 1, 2001; 42(3): 688 - 694. [Abstract] [Full Text]

				S. E. Brooks, X. Gu, S. Samuel, D. M. Marcus, M. Bartoli, P. L. Huang, and R. B. Caldwell Reduced Severity of Oxygen-Induced Retinopathy in eNOS-Deficient Mice Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 222 - 228. [Abstract] [Full Text]

				A. Kawasaki, Y. Otori, and C. J. Barnstable Muller Cell Protection of Rat Retinal Ganglion Cells from Glutamate and Nitric Oxide Neurotoxicity Invest. Ophthalmol. Vis. Sci., October 1, 2000; 41(11): 3444 - 3450. [Abstract] [Full Text]

				J. E Grunwald, A. Iannaccone, and J. DuPont Effect of isosorbide mononitrate on the human optic nerve and choroidal circulations Br. J. Ophthalmol., February 1, 1999; 83(2): 162 - 167. [Abstract] [Full Text]