Therapeutic effect of melatonin on endotoxin-induced uveitis in the golden hamster

SANDE, P; FERNANDEZ, D; CHIANELLI, M.; ALDANA MARCOS, H; ROSENSTEIN, R.; SAENZ, D.

Fort Lauderdale, U.S.A.

Congreso; The Association for Research in Vision and Ophthalmology. 2008; 2008

Purpose: To investigate the therapeutic effect of melatonin on endotoxin-induced uveitis in the golden hamster. Methods: A pellet of 5 mg melatonin was implanted subcutaneously two hours before the intravitreal injection of 1¦Ìg of bacterial lipopolysaccharide (LPS). The effect of melatonin was evaluated in terms of: (i) electron microscopy of the blood-ocular barrier (through a lanthanum tracing analysis), (ii) retinal lipid peroxidation (thiobarbituric acid reactive substances levels were assessed spectrophometricaly), (iii) retinal nitric oxide synthase (NOS) activity (assessed through the conversion of 3H-L-arginine to 3H-L-citrulline, and iv) glial fibrillary acidic protein (GFAP) and vimentin expression (assessed by immunohistochemistry). Results: In LPS-injected eyes, the lanthanum deposits were found filling the spaces between adjacent endothelial cells and between photoreceptor outer segments, indicating a breakdown of inner and outer blood-retinal barriers. Melatonin protected the integrity of both barriers. In melatonin+LPS treated eyes, lanthanum deposits were never observed in the abluminal side of retinal endothelial cells or extending beyond the retinal pigment epithelium. It seems likely that in animals treated with melatonin tight junctions were functional, being capable of preventing extravasations of the tracer through intercellular spaces. LPS increased retinal lipid peroxidation and NOS activity. Both parameters were significantly reduced in the presence of melatonin (p<0.01). In LPS-treated eyes an increase in GFAP immunoreactivity associated with activated retinal astrocytes and M¨¹ller cells was observed. The treatment with melatonin prevented the increase in GFAP expression. Vimentin-immunostaining did not change in any of the experimental groups at both time points. Conclusions: These results support the therapeutic effect of melatonin in experimental uveitis. Moreover, these results suggest that the antioxidant and anti-nitridergic effect of melatonin could be involved in the prevention of LPS-induced retinal damage.