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

Invest Ophthalmol Vis Sci. 1997 Sep;38(10):2038-44.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Count
  • Cell Survival
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Endothelium, Vascular / pathology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • N-Methylaspartate / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / deficiency
  • Nitric Oxide Synthase / drug effects
  • Nitric Oxide Synthase / physiology*
  • Retina / drug effects
  • Retina / enzymology*
  • Retina / pathology
  • Retinal Artery Occlusion / enzymology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / enzymology*
  • Retinal Ganglion Cells / pathology
  • Retinal Vessels / drug effects
  • Retinal Vessels / enzymology
  • Retinal Vessels / pathology


  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • N-Methylaspartate
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester