L-NAME protects against acute light damage in albino rats, but not against retinal degeneration in P23H and S334ter transgenic rats.
Two previous studies have shown that N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of neuronal nitric oxide synthase, protects retinas of albino rats and mice from damaging levels of light. The aims of the present study were two-fold: (1) to confirm the protective effect of L-NAME on wild type albino rats and (2) to determine if L-NAME protects the retinas of transgenic rats with P23H and S334ter rhodopsin mutations. In the first study, albino rats born and raised in 5-10 lux cyclic light were injected intraperitoneally with either L-NAME or its inactive isomer D-NAME 30 min before being placed in bright light (2700 lux) for 24hr. Electroretinograms (ERGs) were recorded before light treatment and 2 days after cessation of exposure, and eyes were enucleated for morphologic evaluation. L-NAME, but not D-NAME provided structural protection of photoreceptor cells from light damage. The functional rescue was not statistically significant between the drug treated groups. In the second study, albino WT, P23H transgenic, and S334ter transgenic rats were born and raised in 400 lux cyclic light. Three week old animals received daily intraperitoneal injections of L-NAME or D-NAME for 4 weeks, and the same drugs were added to their drinking water. At 7 weeks of age, the ERG sensitivity curves and the outer nuclear layer thickness of both transgenic groups were significantly reduced compared to WT controls. However, administration of L-NAME did not protect against retinal degeneration caused by the rhodopsin mutation in either strain of transgenic (P23H and S334ter) rats. Thus, although photoreceptor cell death in light damage and inherited retinal degenerations share a common apoptotic mechanism, there must be significant 'up-stream' differences that allow selective neuroprotection by L-NAME.
Káldi
Ildikó
I
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA.
Dittmar
Mark
M
Pierce
Paula
P
Anderson
Robert E
RE
D016117:Albinism, Ocular / Q000150:complications; D000818:Animals; D030801:Animals, Genetically Modified; D004596:Electroretinography; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D008027:Light; D008297:Male; D009154:Mutation; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000517:prevention & control*; D012243:Rhodopsin / Q000235:genetics
D004791:Enzyme Inhibitors; D012243:Rhodopsin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester