Voluntary exercise preserves visual function and prevents increased inflammatory cytokine expression in an adult mouse model of autosomal dominant retinitis pigmentosa.

Abstract

Purpose : Previous studies support that exercise could potentially be used as a neuroprotective method in patients with retinitis pigmentosa (RP) as well as in animal models of RP. The underlying molecular mechanisms of exercise-induced neuroprotection are elusive. This study investigates the neuroprotective effects of voluntary exercise on retinal structure, function and inflammatory response in an adult mouse model of autosomal dominant retinitis pigmentosa (adRP).

Methods : Adult I307N rhodopsin mice (n=25) were divided into active or inactive groups and received free-spinning or locked running wheels, respectively. After exercising for two weeks, the mice received either a 5-minute period of bright light (“BL”; 6000 lux) or natural light (“dim”; 50 lux). At one and two weeks post-BL, optomotor response (OMR) and electroretinograms (ERG) were measured. After four weeks of exercise, the mice were euthanized and eyes were enucleated for histological and multiplexed cytokine protein expression analysis.

Results : OMR revealed significantly greater spatial frequency and contrast sensitivity thresholds for the active+BL group compared to inactive+BL (p<0.001). Histological analysis showed a preservation of the outer nuclear layer between active+BL and inactive+BL (p=0.007). ERG a- and b-wave amplitudes in active+BL trended higher compared to inactive+BL, however they did not reach statistical significance (p>0.05). Cytokine expression profiles were different for active+BL and inactive+BL animals with trending reductions in interferon gamma-induced protein 10 (IP-10; p=0.085) and keratinocyte-derived chemokine (KC; p=0.093) in active+BL animals, which are involved in chemotactic signaling of microglia and leukocytes.

Conclusions : Our results show that voluntary exercise is protective against retinal degeneration in an adult mouse model of adRP. Exercise preserved visual function and prevented increased expression of inflammatory cytokine expression. These results suggest that exercise regimens should be assessed as a therapeutic intervention to delay progression of RP in patients.

This is a 2021 ARVO Annual Meeting abstract.