Role of Lack of Sleep in the Development of Age-Related Macular Degeneration

In this project, we investigate the potential role of sleep deficiency (SD) in the development of age-related macular degeneration, and how SD reprograms the innate immune system towards destructive neuroinflammation.

Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. Late phases of the disease are marked by retinal degeneration, chronic inflammation and abnormal blood vessel growth. AMD is driven by genetic and environmental factors. An understudied factor that may predispose to neuroinflammatory conditions such as AMD is sleep deficiency (SD), affecting nearly 30% of American adults. Here, we investigate a potential role of SD in choroidal neovascularization associated with AMD and how SD reprograms the innate immune system towards destructive neuroinflammation.

While sleep deficiency (SD) affects nearly 30% of American adults and has well-established effects on inflammation, the link between SD and neuroinflammatory diseases such as AMD has never been studied yet. This project aims to fill this gap. We use an innovative device to induce sleep deprivation that does not induce stress to the mice compared to other devices. We will go further than a phenotypical description of the effect of SD on inflammation and neovascularization. Using cutting-edge technologies, we will look at how SD reprograms immune cells at the epigenetic, transcriptomic and metabolic levels, to allow a precise understanding of the mechanisms.

Our project will provide a framework for a better understanding of the protracted risk factors for AMD progression in patients with a history of altered sleep. Interfering with long term effects of sleep deficiency may have therapeutic potential to treat AMD. It could identify therapeutic avenues to influence the SD-induced epigenetic reprogramming of the innate immune system to hinder the macular degeneration in AMD patients. Our project will also help determine biomarkers expressed by reprogrammed innate immune cells that could be used as diagnostic tools for AMD progression. More broadly, this work could set grounds for public health recommendations to limit onset and progression of AMD.