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; ROMEO, HORACIO E.; SANDE, PABLO H.; ROSENSTEIN, RUTH E.; DORFMAN, DAMIÁN

JOURNAL OF PINEAL RESEARCH

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020 vol. 68 p. 1 - 13

0742-3098

Nonexudative age-related macular degeneration (NE-AMD) represents the lead-ing cause of blindness in the elderly. Currently, there are no available treatmentsfor NE-AMD. We have developed a NE-AMD model induced by superior cervi-cal ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hall-marks. Several lines of evidence strongly support the involvement of oxidative stressin NE-AMD-induced retinal pigment epithelium (RPE) and outer retina damage.Melatonin is a proven and safe antioxidant. Our aim was analysing the effect ofmelatonin in the RPE/outer retina damage within experimental NE-AMD. The treat-ment with melatonin starting 48 h after SCGx, which had no effect on the ubiquitouschoriocapillaris widening, protected visual functions and avoided Bruch ́s membranethickening, RPE melanin content, melanosome number loss, retinoid isomerohydro-lase (RPE65)-immunoreactivity decrease, and RPE and hotoreceptor ultrastructuraldamage induced within experimental NE-AMD exclusively located at the centraltemporal (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 andRPE65-immunoreactivity. These findings suggest that melatonin could become apromising safe therapeutic strategy for NE-AMD.