Melatonin prevents visual and retinal structural alterations induced by early life stress in adult mice

Early life stress (ELS) refers to a prenatal-early postnatal period of social deprivation, neglect, severe trauma, or other adversities, and constitutes a risk factor for developing psychopathologies and different health complications in adulthood. A commonly used model of ELS is maternal separation with early weaning (MSEW), which induces sequelae in adult mouse retinal function and structure. Inflammation and oxidative stress have been involved in ELS long-term consequences. Since melatonin is an effective retinal antioxidant and anti-inflammatory, our aim was to analyze the effect of melatonin in retinal damage induced by MSEW in adult mice. Male and female C57Bl/6J mice were separated from the dams at postnatal days (PND) 4–6, 7–9, 10–12, and 13–16, for 2 h, 3 h, 4 h, and 6 h, respectively, and weaned at PND 17, while control pups were left undisturbed and weaned at PND 21. A pellet of melatonin was subcutaneously implanted in control or MSEW animals at PND 35, while other groups of animals (control or MSEW) underwent sham surgery, without pellet implantation. At PND 60, melatonin preserved scotopic threshold response and photopic negative response amplitudes, contrast sensitivity, phenotypic alterations of microglial cells, and retinal ganglion cell (RGC) number, against MSEW-induced damage. At PND 45, MSEW increased nuclear factor kappa B-subunit p65-, interleukin-1β-, 4-hydroxy-2-nonenal-, and nitrotyrosine-immunoreactivity in the ganglion cell layer. Melatonin prevented the increase in these parameters, as well as in superoxide content in RGC mitochondria induced by MSEW. Melatonin could become a new therapeutic strategy to prevent visual ELS-induced sequelae, one of the threats to life quality resulting from childhood adversities.