Therapeutic Effect of Melatonin on Endotoxin-Induced Uveitis in the Golden Hamster

SANDE, PABLO; FERNANDEZ, DIEGO; CHIANELLI, MONICA; ALDANA MARCOS, HERNAN; ROSENSTEIN RE; SAENZ, DANIEL

Fort Lauderdale, Florida, USA

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

The Association for Research in Vision and Ophthalmology

Abstract 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 vehicle or 1µg 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) glial fibrillary acidic protein (GFAP) and vimentin expression (assessed by immunohistochemistry), iii) retinal lipid peroxidation (thiobarbituric acid reactive substances levels were assessed spectrofluorometricaly), and iv) retinal nitric oxide synthase (NOS) activity (assessed through the conversion of 3H-L-arginine to 3H-L-citrulline. Results:In LPS-injected eyes, 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 the presence of melatonin + LPS, lanthanum deposits were never observed in the abluminal side of retinal endothelial cells or extending beyond the retinal pigment epithelium. In these eyes, functional tight junctions prevented tracer extravasations through intercellular spaces. In LPS-treated eyes an increase in GFAP immunoreactivity associated with activated retinal astrocytes and Müller cells was observed. The treatment with melatonin prevented the increase in GFAP expression. Vimentin-immunostaining did not change among groups. LPS increased retinal lipid peroxidation and NOS activity. Both parameters were significantly reduced in the presence of melatonin (p<0.01). Conclusions:These results indicate that melatonin prevented the disruption of the blood- ocular barrier induced by experimental uveitis. Moreover, these results suggest that the antioxidant and anti-nitridergic effects of melatonin could be involved in the prevention of LPS-induced retinal damage. Key Words: uveitis-clinical/animal model • melatonin