The role of neuronal and endothelial nitric oxide synthase in retinal excitotoxicity.
OBJECTIVE
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.
Vorwerk
C K
CK
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA.
Hyman
B T
BT
Miller
J W
JW
Husain
D
D
Zurakowski
D
D
Huang
P L
PL
Fishman
M C
MC
Dreyer
E B
EB
D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000187:drug effects / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D015356:Retinal Artery Occlusion / Q000201:enzymology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester