June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Utilization of Ketogenic Diet Worsens Visual Deficits in Experimental Optic Neuritis
Author Affiliations & Notes
  • Erin Capper
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    VA Center for Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
  • Jeffrey Anders
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    VA Center for Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
  • Benjamin W Elwood
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    VA Center for Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
  • Randy H Kardon
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    VA Center for Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
  • Oliver W Gramlich
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
    VA Center for Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Erin Capper None; Jeffrey Anders None; Benjamin Elwood None; Randy Kardon None; Oliver Gramlich None
  • Footnotes
    Support  Early Visual Biomarkers of Relapse and Rehabilitation in Multiple Sclerosis, Dept. of Veterans Affairs Office of Research & Development C2978-R
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4085. doi:
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    • Get Citation

      Erin Capper, Jeffrey Anders, Benjamin W Elwood, Randy H Kardon, Oliver W Gramlich; Utilization of Ketogenic Diet Worsens Visual Deficits in Experimental Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4085.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Controversy exists regarding the benefits of ketogenic diet (KD) utilization as adjuvant therapy in multiple sclerosis (MS). The purpose of this study was to establish the effects of KD on visual function and structure in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS-like optic neuritis (ON).

Methods : EAE-ON was induced in 80 female C57BL/6J using MOG33-55, complete Freund’s Adjuvant, and pertussis toxin while another 16 mice served as naïve controls. The EAE induced mice were assigned into cohorts (n=20) to stay on the standard chow (EAE) or to start KD either 2 weeks before induction (pre), at induction (pro), or at symptom onset (late). Mice were scored daily for motor-sensory deficits (mobility scale: 0=normal to 5=death). Visual deficits were assessed using optokinetic responses (OKR) and retinal nerve fiber layer (RNFL) thickness. Pattern electroretinography (pERG) and visual evoked potentials (VEP) were recorded at the end of the experiment. Tissue from the eyes and nervous system were sectioned for histopathology. All data were analyzed using one- and two- way ANOVA followed by post hoc tests.

Results : EAE mice from the pre KD group showed significantly worse motor-sensory deficit relative to EAE controls (AUC EAE score: EAE: 58±2, pre KD: 68±3, p<0.001; pro KD: 60±3, p=0.09; late KD: 58±3). Similarly, visual acuity (VA) data showed worse OKR tracking in the pre KD group (0.23±0.05 cycles/degree (c/deg)) compared to naïve (0.38±0.03 c/deg, p<0.0001) and EAE controls (0.26±0.05 c/deg; p=0.024). There was no significant difference between standard diet EAE mice compared to the pro KD (0.24±0.06 c/deg) and late KD group (0.25±0.05 c/deg), but all three EAE groups had significantly lower VA and EAE scores than the naïve group (p<0.0001). Average RNFL thickness decreased significantly in all EAE induced mice compared to naïve controls (naïve: 69±2µm, EAE: 66±4µm; p=0.001, pre KD: 66±4µm; p=0.002, pro KD: 67±4µm; p=0.02, late KD: 66±3µm; p=0.001) whereas differences between these EAE groups were not significant. Furthermore, all EAE mice showed changes in pERG amplitudes and VEP when compared to naïve mice.

Conclusions : This study identified that implementing KD negatively influenced visual function and structure, and that preconditioning the mice with KD before EAE induction resulted in the worst outcome. These data suggest that KD should not be recommended for patients with MS.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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