April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Altering the gut microbiota ameliorates experimental autoimmune uveitis
Author Affiliations & Notes
  • Yukiko Nakamura
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Christina Metea
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Henry Gruner
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Mark Asquith
    Rheumatology, Oregon Health and Science University, Portland, OR
  • Stephen R Planck
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
    Ophthalmology, Devers Eye Institute, Portland, Oregon, Portland, OR
  • James T Rosenbaum
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
    Ophthalmology, Devers Eye Institute, Portland, Oregon, Portland, OR
  • Phoebe Lin
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Footnotes
    Commercial Relationships Yukiko Nakamura, None; Christina Metea, None; Henry Gruner, None; Mark Asquith, None; Stephen Planck, None; James Rosenbaum, None; Phoebe Lin, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2497. doi:https://doi.org/
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      Yukiko Nakamura, Christina Metea, Henry Gruner, Mark Asquith, Stephen R Planck, James T Rosenbaum, Phoebe Lin; Altering the gut microbiota ameliorates experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2497. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

The gut microbiota appear to be important in the regulation of a number of immune-mediated diseases including multiple sclerosis, diabetes mellitus, and inflammatory bowel disease, but the relationship between the gut microbiome and autoimmune uveitis has not yet been determined. The objective of this study was to investigate whether altering the gut microbiota with broad-spectrum antibiotics affects the severity of experimental autoimmune uveitis (EAU).

 
Methods
 

Interphotoreceptor binding protein (IRBP) peptide 161-180 was used to induce uveitis in B10.RIII mice. Mice were treated with oral or intraperitoneal (ip) antibiotics (1 mg/mL each of ampicillin, neomycin sulfate, and metronidazole, 0.5 mg/mL of vancomycin) starting 1 week prior to antigen challenge. Eyes, spleen, cervical and mesenteric lymph nodes (CLN, MLN), and lamina propia lymphocytes (LPL) were collected on day 20-21. We performed clinical and histological grading of eyes, as well as flow cytometry analysis for quantifying regulatory T-cell (Treg) populations.

 
Results
 

A smaller proportion of antibiotic-fed animals had clinical EAU scores ≥ 2.5 compared with water-fed animals (7.7% vs 46.1%, p=0.048, OR=9.0) (Fig. 1a). The histopathological EAU scores followed a similar trend with 22.2% eyes in the antibiotic-fed group compared to 76.9% eyes in the water-fed group developing a score ≥ 2.5 (p=0.011, OR=11.67, Fig. 1b). No significant difference in scores was found between ip antibiotic compared to ip control groups (clinical: 33% vs. 44.4%, p=0.625, OR=0.629; histopathological: 50% vs 75%, p=0.302, OR=0.33). There were higher proportions of Treg (CD4+, FoxP3+) cells in the CLN, MLN, spleen, and LPL of oral antibiotic-fed mice compared to water-fed mice.

 
Conclusions
 

Our results suggest that alteration of the gut microbiota by oral antibiotic administration modulates the development of EAU. Further investigation of the Treg populations associated with the gut microbial change will be warranted to determine the underlying mechanism.

 
 
Fig. 1. Altering the gut microbiota ameliorates EAU in B10.RIII mice.(A) Clinical scores at peak inflammation (day 13-14) in 3 experiments (n=4-5, each experiment)(B) Histological scores at the end of the experiment (day 20-21) in 2 experiments (n=4-5, each experiment).
 
Fig. 1. Altering the gut microbiota ameliorates EAU in B10.RIII mice.(A) Clinical scores at peak inflammation (day 13-14) in 3 experiments (n=4-5, each experiment)(B) Histological scores at the end of the experiment (day 20-21) in 2 experiments (n=4-5, each experiment).
 
Keywords: 746 uveitis-clinical/animal model • 432 autoimmune disease  
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