Retinal toxicity of nitric oxide released by administration of a nitric oxide donor in the albino rabbit.
OBJECTIVE
Nitric oxide (NO), which has been identified as an endothelium-derived relaxing factor, might be involved in regulation of retinal circulation and intraocular pressure. Recently, it was suggested that NO might also be related to neuronal excitotoxicity mediated by the N-methyl-D-aspartate receptor and to the pathologic changes induced by some kinds of uveitis. However, ocular toxicity of NO released by an NO donor has not been clearly demonstrated. In the current study, NO neurotoxicity in the retina was investigated.


METHODS
S-nitroso-N-acetyl-DL-penicillamine (SNAP, 200 nmol) was injected into the vitreous of albino rabbits as an NO donor. The changes of retinal function were evaluated at 1, 2, and 3 hours and 1 and 4 weeks after SNAP injection, using electroretinogram and visual-evoked potentials. Histologic changes of the retina were also examined.


RESULTS
Injection of SNAP reduced the a-wave amplitude. In contrast, the amplitudes of the oscillatory potentials were increased during the 3-hour observation period. Histologic examination showed vacuolar degeneration and loss of the nuclei of the photoreceptors. In the inner retina, some ganglion cells were lost, and cell density in the internal nuclear layer was decreased.


CONCLUSIONS
Retinal toxicity of NO was demonstrated functionally and histologically, suggesting that NO may play a pathophysiologic role in retinal ischemia or in degenerative retinal diseases.
Oku
H
H
Department of Ophthalmology, Osaka Medical College, Takatsuki, Japan.
Yamaguchi
H
H
Sugiyama
T
T
Kojima
S
S
Ota
M
M
Azuma
I
I
D000818:Animals; D002452:Cell Count; D004596:Electroretinography; D005074:Evoked Potentials, Visual / Q000502:physiology*; D007267:Injections; D009569:Nitric Oxide / Q000008:administration & dosage / Q000633:toxicity*; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000633:toxicity*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine