Running to save sight: The effects of exercise on retinal health and function

Abstract

The benefits of exercise to human health have long been recognised. However, only in the past decade have researchers started to discover the molecular benefits that exercise confers, especially to the central nervous system (CNS). These discoveries include the magnitude of molecular messages that are communicated from skeletal muscle to the CNS. Despite these advances in understanding, very limited studies have been conducted to decipher the molecular benefits of exercise in retinal health and disease. Here, we review the latest work on the effects of exercise on the retina and discuss its effects on the wider CNS, with a focus on demonstrating the potential applicability and comparative molecular mechanisms that may be occurring in the retina. This review covers the key molecular pathways where exercise exerts its effects: oxidative stress and mitochondrial health; inflammation; protein aggregation; neuronal health; and tissue crosstalk via extracellular vesicles. Further research on the benefits of exercise to the retina and its molecular messages within extracellular vesicles is highly topical in this field.

Physical Activity Status and Diabetic Retinopathy: A Review

“…Physical exercise has been postulated to provide a protective effect on retinal health as it has been shown to both lower the risk of age-related macular degeneration and improve visual outcomes [33]. Szalai et al (2020) coined the term "trained eye," similar to the term "trained heart" used in cardiology to emphasize the beneficial effects of physical exercise on not only heart health but also on the visual system as well [34]. In a review conducted by Li et al (2019), they further looked at the protective effects of physical activity on retinal health and found promising beneficial effects for this treatment and preventative modality [35].…”

Voluntary exercise modulates pathways associated with amelioration of retinal degenerative diseases

“…Exercise has well known and documented systemic benefits, including to the CNS and in protection against neurodegenerative Frontiers in Physiology frontiersin.org diseases (reviewed in Chu-Tan et al (2022). Therefore, to investigate the effects of exercise on retinal protection against degeneration, mice either with or without (sedentary) freeaccess to running wheels for 14 or 28 days (14 days in supplementary data), were subjected to PD-induced retinal degeneration.…”

“…Research has shown that exercise is able to regulate systemic inflammation, by modulating key inflammatory pathways and proinflammatory cytokine profiles that lead to downstream dampening of innate immune responses (Nieman and Wentz, 2019;Chu-Tan et al, 2021). In the retina, inflammatory modulation in response to exercise has been correlated with protection against degeneration (Chrysostomou et al, 2016;Mees et al, 2019;Dantis Pereira de Campos et al, 2020;Bales et al, 2022).…”

“…Although these studies collectively shed light on the therapeutic potential of exercise to reduce inflammation and protect against, or slow the progression of, retinal degenerations, knowledge on the precise molecular events occurring within the retina during exercise is still lacking. Clinical research has largely been confined to correlative epidemiological studies, whereas animal studies have been limited to implicative processes and/or based on single, select molecular targets (Chu-Tan et al, 2021). Further, as animal studies to date have predominantly employed a forced model of exercise, it is unclear what potentially confounding effects stress induced shock-forcing methods may have on the results of these studies, with known stress and anxiety-like behaviours exhibited in forced vs. voluntary-exercise animals (Leasure and Jones, 2008) as well as stress having a known impact on inflammation in the retina (Malan et al, 2020).…”

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

“…Neuroprotective strategies include a broad array of approaches that promote neuron survival by preserving their structure and function. A multitude of neuroprotective agents, including antiapoptotic, antioxidant and anti-inflammatory drugs, and rehabilitative methods such as exercise and electrical stimulation, have proven effective in animal models of retinal degeneration and in patients with reduced vision [ 3 , 99 , 100 ]. While none of these agents have been approved by the US Food and Drug Administration as drugs with neuroprotective effects, numerous compounds have been tested in research and in (pre)clinical studies [ 101 , 102 ].…”