Effect of bacterial lipopolysaccharide on ischemic damage in the rat retina.

FRANCO, P.; FERNANDEZ, D; SANDE, P; KELLER SARMIENTO, M; CHIANELLI, M.; SAENZ, D.; ROSENSTEIN, R.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

ASSOC RESEARCH VISION OPHTHALMOLOGY INC

Año: 2008 vol. 49 p. 4604 - 4612

0146-0404

Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4604-12. Epub 2008 Jun 14. Effect of bacterial lipopolysaccharide on ischemic damage in the rat retina. Franco PJ, Fernandez DC, Sande PH, Keller Sarmiento MI, Chianelli M, Sáenz DA, Rosenstein RE. Departamento de Bioquímica Humana, Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Universidad de Buenos Aires, Centro de Estudios Farmacologicos y Botanicos, Buenos Aires, Argentina. Abstract PURPOSE: 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