Research articleA short term high-fat high-sucrose diet in mice impairs optic nerve recovery after injury and this is not reversed by exercise
Introduction
Glaucoma is characterized by the accelerated loss of retinal ganglion cells (RGCs), the innermost neurons of the retina that project axons along the optic nerve to visual centres of the brain. Growing evidence suggests that the susceptibility of RGCs to injury and degeneration can be modified by lifestyle factors. We believe that identifying these protective and risk factors will inform new strategies to stop or slow down RGC loss in diseases like glaucoma.
Western pattern diets, which are characterized by a high intake of fat and sugar, have been putatively associated with higher rates of neurodegenerative brain diseases in humans (reviewed in Francis and Stevenson, 2013). Animal studies demonstrate that diets high in fat and sugar can influence neuronal structure and function in various regions of the brain (Cisternas et al., 2015, Molteni et al., 2002) and exacerbate neuronal loss after injury (Agrawal et al., 2015, Bousquet et al., 2012, Choi et al., 2005, Morrison et al., 2010, Wu et al., 2003). However, there is limited information with respect to how these same dietary patterns impact retinal neurons.
We have demonstrated that aerobic exercise protects RGCs of the mouse eye against dysfunction and cell stress after an insult induced by elevation of intraocular pressure (IOP) (Chrysostomou et al., 2014, Chrysostomou et al., 2016). Recently, it has become evident that exercise can also reverse some of the harmful effects associated with high fat consumption in the CNS. Animal studies found that physical activity protected mice against high-fat diet-induced microglial activation and inflammation in the hypothalamus (Yi et al., 2012); and prevented high-fat diet-induced oxidative stress in the hippocampus and deficits in spatial learning (Molteni, 2004). Whether exercise might be effective in reversing any detrimental effects of diet on retinal neurons has not been studied.
Accordingly, we hypothesized that increased intake of dietary fat and sucrose would exacerbate outcomes after RGC injury and that regular exercise may blunt (or prevent) these harmful effects. To explore this possibility, we tested the impact of feeding mice a modified diet with high levels of fat and sucrose, alone or in combination with increased levels of physical activity, on RGC function and structure in response to acute IOP elevation.
Section snippets
Animals and diet
All animal procedures conformed to the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research, and with the requirements of the Royal Victorian Eye & Ear Hospital Animal Research and Ethics Committee. C57BL/6J mice were housed in a temperature- (22 ± 1 °C), light- (12 h light, 12 h dark) and humidity-controlled (30–40%) environment with free access to food and water. Male and female mice were used equally. At 8 weeks of age mice
A short term non-obesogenic and non-hyperglycaemic high-fat high-sucrose diet
The high-fat high-sucrose (HFS) diet used in this study had a total fat content of 36% fat by weight with carbohydrate content from sucrose only (346 g/kg; Table 1). The control diet was comprised of 7% fat content by weight and 100 g/kg sucrose, with fat substituted for carbohydrate (61% by weight). Mice that were fed a HFS diet for 7 weeks did not exhibit significant increases in body weight relative to mice that were fed the control diet (Fig. 1A). Non-fasting blood glucose levels were in
Discussion
The majority of experimental studies that have investigated the effect of a Western-style diet on neuronal integrity and responses to injury have used models of obesity. Reported increases in the vulnerability of cells to injury with such diets have therefore been attributed to obesity-related effects and complications such as diabetes. In this study, we have shown for the first time that a short term increase in dietary fat and sucrose in mice heightened the sensitivity of RGCs to functional
Funding sources
This work was supported by the National Health and Medical Research Council (Project Grant #1033506); the Dorothy Adele Edols Charitable Trust; The Miller Foundation; and the Ophthalmic Research Institute of Australia. The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian Government.
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