Mechanisms involved in the anti-inflammatory effect of melatonin in experimental uveitis

SANDE PH; DORFMAN D; FERNANDEZ DC; CHIANELLI MS; SÁENZ DA; ROSENSTEIN RE

Denver

Congreso; ARVO Annual Meeting 2015; 2015

Purpose: Uveitis is a prevalent intraocular inflammatory disease. We have previously shown that melatonin not only prevents but also counteracts LPS-induced uveitis in the Syrian hamster. The aim of this work was to identify the mechanisms involved in the anti-inflammatory effect of melatonin administered after the onset of ocular inflammation. Methods: Syrian hamster eyes were intravitreally injected with vehicle or LPS. Melatonin was intraperitoneally supplied every 24 h, starting 12 h or 24 h post-LPS injection. Prostaglandin (PG) E2 and PGF2α levels were assessed (radioimmunoassay) in the aqueous humor. Moreover, retinal nitric oxide synthase (NOS) activity (using 3H-arginine), lipid peroxidation (thiobarbituric acid reactive substance levels), and TNFα levels (enzyme-linked immunosorbent assay) were examined. Light microscopy and immunohistochemistry (Müller cell glial fibrillary acidic protein (GFAP)) were used to evaluate the retinal structure. Results: Concomitantly with an improvement of the clinical score and retinal function (electroretinogram), both treatments with melatonin significantly decreased PG levels in aqueous humor from eyes injected with LPS. Moreover, both treatments with melatonin protected the retinal structure, reduced Müller cell GFAP levels, and the increase in retinal nitric oxide synthase (NOS) activity, lipid peroxidation, and TNFα levels induced by LPS. Conclusions: These results indicate the involvement of aqueous humor prostaglandins, and retinal TNFα levels, NOS activity, and oxidative stress in the attenuation of ocular inflammation induced by LPS, and further support the use of melatonin as a therapeutic resource for uveitis treatment.