Abstract
Introduction: :
Objective: In a previous report, we showed that intravitreal injections of bacterial lipopolysaccharide (LPS) induce a significant protection against light-induced retinal damage. The aim of the present work was to analyze the mechanism involved in this effect of LPS.
Methods: :
Male Wistar rats were intravitreously injected with 3 µg LPS in one eye and vehicle in the contralateral eye. Fifteen min before and 6 h after LPS injection, aminoguanidine (an inhibitor of inducible nitric oxide synthase, 100 mg/kg) was intraperitoneally injected. 5-hydroxidecanoic acid (5HD, a mitochondrial K+ ATP channel blocker, 40 mg/kg) was intraperitoneally injected 15 min before LPS, whereas wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor, which supress autophagy, 2µl, 0.2 mM) was injected in the vitreous. One day after injections, rats were placed for 24 h in an open white acrylic box of 60 cm x 60 cm x 60 cm with 10 halogen lamps (10 V 50 W each) located on top. White light spectrum was used, and lighting level was 10,000 lux. The lighting box was kept in an air-conditioned room, and temperature was monitored and maintained at 24°C. All the animals received food and water ad libitum. Subsequently, 7 or 14 days after light exposure, rats were subjected to electroretinography and histological analysis.
Results: :
Constant light for 24 h induced a significant decrease in scotopic ERG a- and b-wave amplitude. The light-induced decrease in both a- and b-wave amplitude was significantly lower in eyes treated with 3µg LPS both at 7 and 14 days after light exposure. Moreover, significant alterations in the outer nuclear and the outer plexiform layers and the pigment epithelium were observed in eyes exposed to constant light. The injection of LPS reduced light-induced photoreceptor degeneration and protected the outer plexiform layer and the pigment epithelium.The injection of wortmannin (but not of aminoguanidine or 5HD) prevented the functional and histological protection induced by LPS against light-induced damage.
Conclusions: :
These results suggest that functional and histological protection against the deleterious effects of constant light provided by LPS involves a PI3K/autophagy dependent mechanism.
Keywords: retina • neuroprotection • radiation damage: light/UV