Low Doses of Bacterial Lipopolysaccharide Inducers Ischemic Preconditioning in the Rat Retina

Abstract

Purpose: : The aim of this study was to investigate whether bacterial lipopolysaccharide (LPS) induce ischemic preconditioning in the retina, as well as the involvement of nitric oxide synthase (NOS) in this mechanism.

Methods: : Rats were intravitrealy injected with different doses of LPS (0.1, 1, and 5 µg) in one eye and vehicle in the contralateral eyes 24 h prior to retinal ischemia induced by increasing intraocular pressure to 120 mmHg for 45 min.The effect of LPS per se was evaluated in terms of protein concentration and cell number in the aqueous humor, at 24 h post-injection. Seven days after ischemia, rats were subjected to flash electroretinography and histological analysis. One group of animals received an intraperitoneal injection of a NOS inhibitor, L-NAME (50 mg/kg), 30 min before the injection of vehicle or LPS. Retinal NOS activity was assessed through the conversion of ³H-L-arginine to ³H-L-citrulline.

Results: : After 24 h of injection, 1 and 5, but not 0.1 µg LPS induced a significant increase in protein levels and cell number in aqueous humor, but the effect of 5 µg on both parameters was significantly higher than that of 1 µg LPS. LPS per se did not affect flash ERG at any doses examined after 24 h of injection. Ischemia for 45 min and reperfusion for 7 days induced a significant decrease in scotopic ERG a- and b-wave amplitude. The ischemic-induced decrease in both a- and b-wave amplitude did not change in eyes receiving 0.1 µg LPS, was significantly lower in eyes treated with 1µg LPS (p<0.01), and was significantly higher in eyes receiving 5 µg LPS (p<0.01). Moreover, 1µg LPS afforded morphologic protection on ischemic-induced damage, as shown by the differences in the thickness of retinal layers. L-NAME, which did not show effects per se, significantly prevented the preconditioning induced by LPS (p<0.01). A significant increase in retinal NOS activity was observed in eyes injected with 1 or 5 µg LPS, but this increase was significantly higher with 5 µg LPS than with 1 µg LPS.

Conclusions: : For the first time, these results indicate that low doses of LPS provide retinal protection against ischemic injury, probably through a NOS-dependent mechanism.

Keywords: retina • ischemia