Age-related Macular Degeneration (AMD) is one of the leading causes of blindness and its advanced stage is characterised by choroidal neovascularisation (CNV) invading the neural retina. Limited treatment options for CNV exist but exercise is emerging as a non-invasive treatment strategy. Here we utilise animal models to understand the molecular mechanisms driving the protective effect of exercise.
This project combines a voluntary running wheel mouse model of exercise with a laser-induced CNV model to unravel the transcriptomic changes resulting from voluntary exercise. Following 28 days of voluntary exercise, CNV laser lesions were induced, then total RNA was isolated from both the retina and the choroid and subjected to RNA sequencing. RNA sequencing was performed at 3 and 7 days post-lesion. We report on both the retinal and choroidal mRNA/microRNA changes that occur and perform pathways analysis to uncover the biological processes that mediate neovascularisation and underly the protective effect of exercise. The timepoints for transcriptomic analysis were consistent with the presence of active neovascularisation validated through measurements of lesion size and fluorescent angiography, and the infiltration of immune cells validated through Iba1 immunolabelling.
This work uncovers the molecular basis of the benefits of exercise in CNV and allows for the development of the next generation of RNA therapeutics for potential use in helping to slow or stop the progression of AMD.