Light environment influences developmental programming of the metabolic and visual systems in mice

Abstract

PURPOSE. Light is a salient cue that can influence neurodevelopment and the immune system. Light exposure out of sync with the endogenous clock causes circadian disruption and chronic disease. Environmental light exposure may contribute to developmental programming of metabolic and neurological systems but has been largely overlooked in Developmental Origins of Health and Disease (DOHaD) research. Here, we investigated whether developmental light exposure altered programming of visual and metabolic systems. METHODS. Pregnant mice and pups were exposed to control light (12:12 light:dark) or weekly light cycle inversions (circadian disruption [CD]) until weaning, after which male and female offspring were housed in control light and longitudinally measured to evaluate differences in growth (weight), glucose tolerance, visual function (optomotor response), and retinal function (electroretinogram), with and without high fat diet (HFD) challenge. Retinal microglia and macrophages were quantified by positive Iba1 and CD11b immunofluorescence. RESULTS. CD exposure caused impaired visual function and increased retinal immune cell expression in adult offspring. When challenged with HFD, CD offspring also exhibited altered retinal function and sex-specific impairments in glucose tolerance. CONCLUSIONS. Overall, these findings suggest that the light environment contributes to developmental programming of the metabolic and visual systems, potentially promoting a pro-inflammatory milieu in the retina and increasing the risk of visual disease later in life.