Bacterial lipopolysaccharide induces ischemic tolerance in the rat retina

FRANCO PABLO J; FERNANDEZ DIEGO C; SANDE PABLO; KELLER SARMIENTO MARIA; CHIANELLI MONICA; SAENZ DANIEL; ROSENSTEIN RUTH E

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

Association For Research In Vision And Ophthalmology (Arvo)

Lugar: Rockville, MD ; Año: 2008 vol. 49 p. 4604 - 4612

0146-0404

Purpose: The aim 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 intravitrealy injected with different doses of LPS (0.1, 1 or 5 ìg) in one eye and vehicle in the contralateral eye 24 h prior to retinal ischemia induced by increasing intraocular pressure to 120 mm Hg for 40 or 60 min. Subsequently, 7 or 14 days after ischemia, rats were subjected to electroretinography and histological 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 3H-L-arginine to 3H-L-citrulline. Results: One ìg LPS (but not 0.1 or 5 ìg) afforded significant morphologic and functional protection in eyes exposed to ischemia/reperfusion injury. The beneficial effect of LPS was reversed by the treatment with L-NAME, aminoguanidine, or W1400. LPS (1 and 5, but not 0.1 ìg) significantly increased retinal NOS activity. Conclusions: These results indicate that LPS provides retinal protection against ischemic/reperfusion injury in a dose-dependent manner, probably through an inducible NOS -dependent mechanism.