Melatonin protects the retina from experimental nonexudative age‐related macular degeneration in mice

DIÉGUEZ, HERNÁN H.; GONZÁLEZ FLEITAS, MARÍA F.; ARANDA, MARCOS L.; CALANNI, JUAN S.; KELLER SARMIENTO, MARÍA I.; CHIANELLI, MÓNICA S.; ALAIMO, AGUSTINA; SANDE, PABLO H.; ROMEO, HORACIO E.; ROSENSTEIN, RUTH E.; DORFMAN, DAMIÁN

JOURNAL OF PINEAL RESEARCH

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020 vol. 68

0742-3098

Nonexudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. Currently, there are no available treatments for NE-AMD. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks. Several lines of evidence strongly support the involvement of oxidative stress in NE-AMD-induced retinal pigment epithelium (RPE) and outer retina damage. Melatonin is a proven and safe antioxidant. Our aim was analysing the effect of melatonin in the RPE/outer retina damage within experimental NE-AMD. The treatment with melatonin starting 48 h after SCGx, which had no effect on the ubiquitous choriocapillaris widening, protected visual functions and avoided Bruch´s membrane thickening, RPE melanin content, melanosome number loss, retinoid isomerohydrolase (RPE65)-immunoreactivity decrease, and RPE and hotoreceptor ultrastructural damage induced within experimental NE-AMD exclusively located at the central temporal (but not nasal) region. Melatonin also prevented the increase in outer retina/RPE oxidative stress markers and a decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, when the treatment with melatonin started at 4 weeks post-SCGx, it restored visual functions and reversed the decrease in RPE melanin content and RPE65-immunoreactivity. These findings suggest that melatonin could become a promising safe therapeutic strategy for NE-AMD.