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

SANDE PH; DORFMAN D; SILBERMAN DM; FERNADEZ DC; CHIANELLI MS; SÁENZ DA; ROSENSTEIN RE

Denver, Colorado

Congreso; Annual Meeting ARVO; 2015

Association For Research In Vision And Ophthalmology (Arvo)

June 2015 Volume 56, Issue 7 Meeting Abstract  |   June 2015Mechanismsinvolved in the anti-inflammatory effect of melatonin in experimental uveitisPablo Sande; Damian Dorfman; Magali Silberman; Diego Fernandez; Monica Chianelli; Daniel Saenz; Ruth Estela Rosenstein Author Affiliations & Notes Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3099. doi:  AbstractPurpose: Uveitis is a prevalent intraocularinflammatory disease. We have previously shown that melatonin not only preventsbut also counteracts LPS-induced uveitis in the Syrian hamster. The aim of thiswork was to identify the mechanisms involved in the anti-inflammatory effect ofmelatonin administered after the onset of ocular inflammation.Methods: Syrian hamster eyes wereintravitreally injected with vehicle or LPS. Melatonin was intraperitoneallysupplied every 24 h, starting 12 h or 24 h post-LPS injection. Prostaglandin(PG) E2 and PGF2αlevels were assessed (radioimmunoassay) in the aqueous humor. Moreover, retinalnitric oxide synthase (NOS) activity (using 3H-arginine), lipid peroxidation(thiobarbituric acid reactive substance levels), and TNFα levels (enzyme-linked immunosorbentassay) were examined. Light microscopy and immunohistochemistry (Müller cellglial fibrillary acidic protein (GFAP)) were used to evaluate the retinalstructure.Results: Concomitantly with an improvementof the clinical score and retinal function (electroretinogram), both treatmentswith melatonin significantly decreased PG levels in aqueous humor from eyesinjected with LPS. Moreover, both treatments with melatonin protected theretinal structure, reduced Müller cell GFAP levels, and the increase in retinalnitric oxide synthase (NOS) activity, lipid peroxidation, and TNFα levels induced by LPS.Conclusions: These results indicate theinvolvement of aqueous humor prostaglandins, and retinal TNFα levels, NOS activity, and oxidativestress in the attenuation of ocular inflammation induced by LPS, and furthersupport the use of melatonin as a therapeutic resource for uveitis treatment.TheAssociation for Research in Vision and Ophthalmology