Melatonin as a therapeutic resource for uveitis treatment

ROSENSTEIN, RUTH; FERNANDEZ, DIEGO; SAENZ, DANIEL; CHIANELLI, MÓNICA; DEL SOLE MARÍA JOSÉ; SANDE, PABLO

Advances in Medicine and Biology. Volume 65

Nova Science Publishers

Lugar: New York; Año: 2013; p. 25 - 46

Melatonin as a therapeutic resource for uveitis treatment Kukner et al. (2006) and Sande et al. (2008) investigated the effectiveness of melatonin as a therapeutic strategy in uveitis. In the Kukner study, intravitreal injections of bovine serum albumin were used to induce uveitis in the guinea pig. Melatonin, vitamin E, or aprotinin were intraperitoneally administered 3 days after albumin injection. A significant increase in leptin expression occurs in the retina, choroid, sclera, and episclera; ganglion cells were edematous and inner plexiform layer thickness increased in uveitic eyes. In animals treated with melatonin, vitamin E, or aprotinin, leptin expression was similar to the control group and edema and histopathological changes were reduced (Kukner et al., 2006). Sande et al. studied EIU, another established experimental model for uveitis, giving a single intravitreal injection of LPS in the golden hamster. In this study, a pellet of melatonin was implanted subcutaneously 2 h before the intravitreal injection of LPS. Twenty-four hours and 8 days after injection, the inflammatory response was evaluated in terms of: (i) integrity of BOB, (ii) clinical signs, (iii) histopathological studies, and (iv) retinal function. Melatonin reduced the leakage of proteins and cells in the anterior segment of LPS-injected eyes, decreased clinical signs, and protected the ultrastructure of BOBs. In animals injected with LPS, a remarkable disorganization of rod outer segment membranous disks was observed, whereas no morphological changes in photoreceptor outer segments were observed in animals treated with LPS plus melatonin. Furthermore, melatonin prevented the decrease in the ERG activity induced by LPS. Melatonin significantly abrogated the LPS-induced increase in retinal NOS activity, TNFa, and nuclear factor kB (NFkB) p50 and p65 subunits levels (Sande et al., 2008). These results indicate that melatonin prevents clinical, biochemical, histological, ultrastructural, and functional consequences of experimental uveitis in hamsters, probably through an NFkB-dependent mechanism. Based on these results, we examined the effect of melatonin on experimetally-induced feline uveitis. For this purpose, melatonin was orally administered every 24 hr to a group of ten cats, from 24 h before until 45 days after intravitreal injections of vehicle or LPS (Del Sole et al., 2012). Eyes were evaluated by means of clinical evaluation, intraocular pressure (IOP), BOB integrity (via measurement of protein concentration and cell content in samples of AH), ERG, and histological examination of the retinas. The treatment with melatonin significantly decreased clinical signs and prevented the reduction in IOP induced by LPS. In LPS-injected eyes, melatonin significantly preserved the BOB integrity, as shown by a decrease in the number of infiltrating cells and protein concentration in the AH. Mean amplitudes of scotopic ERG a- and b-waves were significantly reduced in eyes injected with LPS, whereas melatonin significantly prevented the effect of LPS. At 45 days after injection, LPS induced alterations in photoreceptors and at the middle portion of the retina, whereas melatonin preserved the retinal structure. These results indicate that melatonin prevented clinical, biochemical, functional, and histological alterations induced by LPS injection in cats (Del Sole et al., 2012). Thus, melatonin might constitute a useful tool for the treatment of feline uveitis.