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Darren J Lee, Fauziyya Y Muhammad, Dawei Wang; Obesity Exacerbates Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2552.
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© ARVO (1962-2015); The Authors (2016-present)
Rates of obesity are increasing in developed countries. Mirroring this trend is an increase in the incidence and prevalence of autoimmune disease. Experimental autoimmune uveoretinitis (EAU) is a widely used murine model of human autoimmune uveitis that resolves with post-EAU regulatory immunity in the spleen that provides resistance to relapse. It is thought that a lack of this regulatory immunity contributes to relapsing autoimmune uveitis. As such, this study investigates the role that obesity has with autoimmune uveitis and the impact of obesity on the induction of post-EAU regulatory immunity.
C57BL/6J mice were fed a high fat diet (HFD) consisting of 45% or 60% calories derived from fat or a normal fat diet (NFD) consisting of 11% calories derived from fat. Two weeks after the mice were started on the HFD they were immunized for EAU. The body weight, blood glucose (BG), food consumption, and the retina was clinically evaluated for signs of uveitis. Spleen cells from post-EAU mice (80-90 days after immunization) were collected, re-stimulated with IRBPp 1-20 (IRBP), and transferred to recipient mice immunized for EAU to determine the induction of functional regulatory immunity.
Food consumption was slightly lower in HFD groups, but an increase in weight compared to NFD groups demonstrated a total increase in net caloric intake. Body weight did not change with EAU for either HFD group compared to NFD. Compared with NFD EAU mice the EAU mice on a 45% HFD showed slightly lower fasting BG, but the 60% HFD EAU mice had significantly higher BG. EAU resolved at a similar tempo compared with NFD mice, but the maximum severity was significantly greater in both groups with slightly more severe scores in the 60% HFD mice. Transfer of post-EAU spleen cells from HFD mice into recipient mice showed no suppression of EAU.
These results show that EAU may provide some protection from diabetes in a type 2 diabetes model. Further, we show that HFD exacerbates EAU and impairs the induction of ocular autoantigen specific regulatory immunity. These observations demonstrate that obesity may contribute to the severity and prevalence of autoimmune uveitis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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