Carbohydrate restriction preserves visual acuity and motor function in a mouse model of autoimmune demyelination

Abstract

Purpose : Ocular pathologies are understudied sequelae of multiple sclerosis (MS) and other autoimmune diseases. Current treatments are expensive, highly immunosuppressive drugs that increase infections and cause other adverse effects but are only partially efficacious. The goal of this study was to test the hypothesis that a well-formulated ketogenic diet (WF-KD) can reduce optic neuritis and preserve vision in a mouse model of MS called experimental autoimmune encephalomyelitis (EAE).

Methods : Male and female C57BL/6J mice were fed the WF-KD (77.1% fat, 22.4% protein, 0.5% carbohydrate) or a nutrient-matched control diet (10.4% fat, 20.4% protein, 69.3% carbohydrate) and 2 weeks later immunized with a myelin oligodendrocyte glycoprotein peptide antigen to induce EAE. Motor deficits, visual acuity, as well as glucose and ketone levels in blood were measured longitudinally. Post-mortem, retinal ganglion cells (RGCs) were quantified and splenocytes were immuno-profiled. Circulating cytokines and fatty acid content were also analyzed.

Results : Unlike obesogenic western diets containing pro-inflammatory fats and high carbohydrate content, EAE mice fed a WF-KD did not gain weight. The WF-KD conferred resistance to EAE motor deficits and preserved RGCs and visual acuity. Analysis of plasma showed that the WF-KD decreased circulating C-reactive protein and proinflammatory cytokines, reduced pro-inflammatory omega-6 fatty acids (e.g., arachidonic acid), and increased anti-inflammatory omega-3 fatty acids.

Conclusions : These findings demonstrate that a diet enriched in healthy fats and restricted for carbohydrates promotes a systemic anti-inflammatory milieu that mitigates autoimmune-induced visual and motor deficits, further supporting ongoing clinical trials testing this dietary strategy to treat MS patients.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.