Voluntary exercise attenuates choroidal neovascularization in mice

Abstract

Purpose : Although meta-analyses of human subjects have found a potential relationship between physical activity and age-related macular degeneration (AMD), there have been to date no studies performed in an experimental setting. Here, we tested the hypothesis that voluntary exercise-trained mice exhibit less severe choroidal neovascularization (CNV) in a laser photocoagulation model.

Methods : Age- and sex-matched mice were singly housed in cages with or without running wheels. Exercise mice ran for 28 days. On day 29 all mice were subjected to laser photocoagulation to induce CNV. Mice were returned to respective cages and were either sedentary or exercised for six days. Eyes were then processed for either posterior pole flatmounting or cryosectioning followed by confocal microscopy. Flatmounts were stained with IB4-lectin and anti-F4/80 antibody; fluorescent in situ hybridization was used to probe sections for Ccl2, Il6, and Vegfa mRNA. CNV volume was calculated using an established protocol on ImageJ. Mann-Whitney U test was used to determine statistical significance of CNV volume and F4/80⁺ abundance between sedentary and exercised mice.

Results : We observed a 39% (P=0.17) and 32% (P=0.029) reduction in CNV volume across two replication studies. Overall, CNV volume was reduced by 37% (P=0.0098). Exercise-trained male and female mice exhibited similar CNV volume (P=0.99). Average daily distance did not strongly correlate with CNV volume (R=-0.11, P=0.80), although we did observe a slight negative relationship between post-surgery run distance and CNV volume (R=-0.21, P=0.64). F4/80⁺ immune cell infiltration showed a marked reduction of 72% in CNV lesions of exercise-trained mice compared to sedentary (P=0.037). Ccl2, Il6, and Vegfa mRNA were less abundant in exercise-trained mice retinae.

Conclusions : Voluntary exercise was beneficial in attenuating CNV volume and F4/80⁺ immune cell infiltration. These experimental findings corroborate epidemiological studies that have previously reported an ameliorative effect of exercise on ocular pathologies. It is interesting to note that exercise has been reported to increase angiogenesis in skeletal muscle and adipose tissue. Thus, future studies will be required to delineate the mechanism by which exercise reduces ocular neovascularization.

This is a 2020 ARVO Annual Meeting abstract.