Short-Term Combined Exercise Improves Inflammatory Profile in the Retina of Obese Mice

Abstract

Excess of adipose tissue increases the concentration of proinflammatory cytokines, triggering a subclinical inflammatory condition. This inflammatory profile contributes to retina damage, which can lead to retinal dysfunction and reduced vision. Regularly practicing both aerobic and strength exercises is well known for promoting anti-inflammatory effects on different organs in the peripheral and central regions. However, the effects of combined physical exercise (CPE; strength + aerobic) on the inflammatory process in the retina tissue are not yet known. This study aimed to investigate the effects of CPE on the inflammatory profile of the retina in obese mice. Swiss mice were distributed into control, sedentary obese, and trained obese groups. The trained obese group was subjected to short-term CPE, 1 h/day, for 7 days. The CPE was composed of aerobic and strength exercises in the same exercise session. The strength exercise protocol consisted of 10 climbing series, with 12 ± 1 dynamic climbing movements at 70% of the maximum voluntary carrying capacity (MVCC), and the aerobic exercise protocol consisted of 30 min of treadmill running, with an intensity of 75% of the exhaust velocity. Subsequently, the retina was excised and analyzed by Western blot. Obese animals presented impairment on glucose homeostasis and elevated levels of proinflammatory proteins in the serum and retina; however, CPE was effective in reversing these parameters, independently of changes in body adiposity. Therefore, for the first time, we have shown that short-term CPE can be an important strategy to treat an inflammatory profile in the retina.

Physical Activity Status and Diabetic Retinopathy: A Review

“…Across 85 survey sites, they included 1909 participants in their investigation, and they found that DR was the second leading cause of blindness and visual impairment after cataracts. Blindness and moderate-tosevere visual impairment were high within the studied population for both conditions, and they cited many risk factors, which included physical inactivity[50]. Frith and Loprinzi et al (2018) investigated the impact of nonbouted, or lifestyle versus bouted, or structured form of physical activity on retinopathy prevalence and its severity among a selected cohort.…”

Voluntary exercise modulates pathways associated with amelioration of retinal degenerative diseases

“…There is a strong link between exercise and the inflammatory system in the human body including in the CNS (Nieman and Wentz, 2019). Exercise is known to modulate key inflammatory mechanisms, mitigating and regulating systemic inflammation in neurological diseases such as multiple sclerosis (Dalgas et al, 2012), systemic lupus erythematous (Perandini et al, 2012), Alzheimer's and Parkinson's diseases (Fuller et al, 2020), and preclinical models of retinal degeneration (Crowston et al, 2017;Sellers et al, 2019;Zhang et al, 2019;Dantis Pereira de Campos et al, 2020). However, these antineuroinflammatory effects, whilst observed, have not been wellsubstantiated or often investigated past single target identification.…”

“…To date, the majority of animal studies investigating the effect of exercise in the retina have used forced exercise models where an often unpleasant or painful stimulus is used to ensure the animals complete a defined amount of physical activity (Ji et al, 2013;Kim et al, 2013;Chrysostomou et al, 2014;Lawson et al, 2014;Chrysostomou et al, 2016;Allen et al, 2018;Mees et al, 2019;Dantis Pereira de Campos et al, 2020). While it is understandable that studies using forced-exercise models use this method in an attempt to ensure equal and consistent levels of desired exercise, output measures from our study revealed that mice would voluntarily and consistently utilize the running wheels, running large distances of 10.2 km/day on average, mitigating any need to force this seemingly natural behavior onto them.…”

“…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). In rodent models of retinitis pigmentosa, voluntary exercise has been shown to be effective against photoreceptor cell loss and inflammation as well as increase visual acuity (Barone et al, 2012;Barone et al, 2014;Zhang et al, 2019), while swimming used in a model of glaucoma was protected against astrocytic gliosis, macrophage activation and age-related vulnerability (Chrysostomou et al, 2014).…”

“…In rodent models of retinitis pigmentosa, voluntary exercise has been shown to be effective against photoreceptor cell loss and inflammation as well as increase visual acuity (Barone et al, 2012;Barone et al, 2014;Zhang et al, 2019), while swimming used in a model of glaucoma was protected against astrocytic gliosis, macrophage activation and age-related vulnerability (Chrysostomou et al, 2014). Furthermore, treadmill exercise was shown to protect visual function, and decrease inflammation and apoptotic neuronal cell death in a model of diabetic retinopathy (Ji et al, 2013;Kim et al, 2013;Allen et al, 2018;Dantis Pereira de Campos et al, 2020). Finally, in a light-induced model of degeneration that recapitulates aspects of atrophic AMD (Natoli et al, 2016), forced treadmill exercise in albino mice was shown to preserve both retinal morphology and function (Lawson et al, 2014;Mees et al, 2019) with low-intensity exercise proving the most beneficial (Mees et al, 2019).…”