Retinal neurotoxicity of nitric oxide donors with different half-life of nitric oxide release: involvement of N-methyl-D-aspartate receptor.
We compared the degree of neurotoxic outcome in the retina exposed to three nitric oxide (NO) donors with different half-life of NO release. Intravitreal injection of NO donors resulted in a significant decrease in cell density in the ganglion cell layer and thinning of the inner plexiform layer in a half-life time-dependent manner. Concurrent injection of an NO-trapping reagent with an NO donor abolished NO donor-induced retinal damage. (+)-MK-801 also prevented NO-induced retinal damage, indicating that N-methyl-D-aspartate receptors are partly involved in NO-induced neurodegeneration. These results may be relevant to a pathogenic role of NO - glutamate receptor in several ophthalmic disorders.
Takahata
Kazue
K
Institute of Research and Development, Fujimoto Pharmaceutical Corporation, Osaka, Japan.
Katsuki
Hiroshi
H
Kume
Toshiaki
T
Ito
Ken
K
Tochikawa
Yoshinaga
Y
Muraoka
Shizuko
S
Yoneda
Fumio
F
Kashii
Satoshi
S
Honda
Yoshihito
Y
Akaike
Akinori
A
D000818:Animals; D006207:Half-Life; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000493:pharmacokinetics / Q000633:toxicity*; D009603:Nitroso Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
C118603:NOC 12; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide