THERAPEUTIC EFFECT OF MELATONIN ON ENDOTOXIN-INDUCED UVEITIS IN THE GOLDEN HAMSTER

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

Buenos Aires, Argentina

Congreso; XVII International Congress of Eye Research; 2006

The International Society of Eye Research

Uveitis is an inflammatory process that affects primary the uveal tract, but may reach the retina, causing a deficit of visual function. The disease is mainly due to the damage generated by leukocyte infiltration which releases cytokines and other inflammatory mediators, like arachidonic acid metabolites, reactive oxygen species, nitric oxide (NO), and superoxide anion, among others. Several evidences support that melatonin inhibits the retinal nitridergic pathway activity, decreases the synthesis of prostaglandins and is a potent antioxidant. We have developed an experimental model of uveitis in golden hamsters through the intravitreal injection of bacterial lipopolysaccharide (LPS). The aim of this work was to examine the therapeutic effect of melatonin on endotoxin-induced uveitis. For this purpose, melatonin was administered through a subcutaneous pellet of 20µg. Clinical observation (conjuntival hyperemia, alterations of episcleral vessels, cornea, iris, crystalline and posterior segment) was analyzed by assigning a score to each of these signs (maximum: 16 points). In order to evaluate the state of the hemato-ocular barrier, the number of infiltrating cells and protein content were assessed in aqueous humor. In addition, retinal nitric oxide synthase (NOS) activity was measured through the conversion of 3H-arginine to 3H-citrulline. To analyze retinal function, electroretinograms were registered in scotopic conditions. The results indicate that melatonin decreased the clinical score (LPS vs melatonin + LPS, p<0.05, Mann Whitney´s test) and it significantly reduced the concentration of proteins and the number of infiltrating cells. Retinal NOS activity significantly decreased in the presence of melatonin. In addition, the methoxyindole reverted the decrease in ERG a- and b-wave amplitude induced by LPS (LPS vs melatonin + LPS, p< 0.01, Tukey´s test). In summary, these results indicate that melatonin significantly reduced clinical, biochemical, and functional alterations induced by LPS. Therefore, melatonin could be considered a new therapeutic strategy in uveitis treatment.