Effect of bacterial lipopolysaccharide on ischemic damage in the rat retina.
OBJECTIVE
The purpose of this study was to investigate whether bacterial lipopolysaccharide (LPS) induces ischemic preconditioning in the rat retina, and, if so, whether nitric oxide (NO) is involved in this process.


METHODS
Rats were intravitreously injected with different doses of LPS (0.1, 1, or 5 microg) in one eye and vehicle in the contralateral eye 24 hours before retinal ischemia induced by increasing intraocular pressure to 120 mm Hg for 40 or 60 minutes. Subsequently, 7 or 14 days after ischemia, the rats were subjected to electroretinography and histologic analysis. One group of animals received intraperitoneal injections of NOS inhibitors, N-nitro-L-arginine methyl ester (L-NAME) aminoguanidine or N-(3-(aminomethyl)benzyl)acetamidine (W1400) before the injection of LPS or vehicle. Retinal nitric oxide synthase (NOS) activity was assessed through the conversion of (3)H-L-arginine to (3)H-L-citrulline.


RESULTS
One microgram (but not 0.1 or 5 microg) LPS afforded significant morphologic and functional protection in eyes exposed to ischemia-reperfusion injury. The beneficial effect of LPS was reversed by treatment with L-NAME, aminoguanidine, or W1400. LPS (1 and 5 microg, but not 0.1 microg) significantly increased retinal NOS activity.


CONCLUSIONS
These results indicate that LPS provides retinal protection against ischemia-reperfusion injury in a dose-dependent manner, probably through an inducible NOS-dependent mechanism.
Departamento de Bioquímica Humana, Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Universidad de Buenos Aires, Centro de Estudios Farmacologicos y Botanicos, Buenos Aires, Argentina.
Pablo J
PJ
Franco
Diego C
DC
Fernandez
Pablo H
PH
Sande
María I
MI
Keller Sarmiento
Mónica
M
Chianelli
Daniel A
DA
Sáenz
Ruth E
RE
Rosenstein
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines; D007267:Injections; D019194:Ischemic Preconditioning; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000503:physiopathology*; D012486:Salmonella typhimurium; D014822:Vitreous Body
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine