June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Probiotics pretreatment attenuates impaired corneal re-epithelialization in diabetic mice through amelioration of T cell immunity and remodulation of the intestinal microbiome
Author Affiliations & Notes
  • Yashan Bu
    The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
  • Sheng Xu
    The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
  • Yau Kei Chan
    The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
  • Amy CY Lo
    The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
  • Joshua Wing-Kei Ho
    The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
  • Kendrick Co Shih
    The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
  • Footnotes
    Commercial Relationships   Yashan Bu None; Sheng Xu None; Yau Kei Chan None; Amy Lo None; Joshua Wing-Kei Ho None; Kendrick Shih None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3653 – A0218. doi:
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      Yashan Bu, Sheng Xu, Yau Kei Chan, Amy CY Lo, Joshua Wing-Kei Ho, Kendrick Co Shih; Probiotics pretreatment attenuates impaired corneal re-epithelialization in diabetic mice through amelioration of T cell immunity and remodulation of the intestinal microbiome. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3653 – A0218.

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

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Abstract

Purpose : 1) To compare corneal re-epithelialization rates, ocular surface and systemic T cell immunity after corneal alkali burn injury between probiotics- or vehicle (PBS) -pretreated Akita (diabetic) and wild type (WT) mice.
2) To compare gut microbiota between probiotics- or PBS-pretreated diabetic and WT mice at baseline and 72 hours after corneal alkaline burn injury and to correlate this with the findings of systemic and ocular surface immunity

Methods : Heterozygous Ins2Akita mice were used as a mouse model of Type I diabetes, with WT C57BI6/J mice serving as controls. Probiotics IRT5 or PBS was administered to the mice by oral gavage continuously for 14 days before the corneal alkaline burn injury. At day 15, alkaline burn was induced on the right eye of mice under general anesthesia. Immediately after injury and on post-injury day 3, the cornea was examined with slit lamp with fluorescein stain under cobalt blue light. T cell profiles on the ocular surface and in the peripheral blood were analyzed by flow cytometry. Intestinal microbiome was characterized by shotgun metagenomics sequencing.

Results : Probiotics pretreatment has restored the delayed corneal wound healing in diabetic mice. In the peripheral blood and on the ocular surface, significantly elevated levels of CD4+ T cells were seen in PBS-pretreated WT mice and probiotics-pretreated WT and diabetic mice, but were not seen in PBS-pretreated diabetic mice. On post-injury day 3, the gut microbiome of diabetic mice had higher alpha diversity in the PBS-pretreated groups but not in the probiotics-pretreated groups. In the probiotics-pretreated diabetic mice, we observed increased Muribaculaceae and Enterococcus faecalis, and reduced Lactobacillus johnsonii and Bacteroides at baseline compared to vehicle pretreated ones. The baseline and post-injury differences in gut microbiome are potentially linked to the altered T cell immunity in diabetic mice, suggesting the immunomodulatory effects of probiotics.

Conclusions : Probiotics pretreatment attenuated the impaired corneal wound healing response after injury in diabetic mice. The ameliorated T cell immunity and remodulated gut microbial composition with probiotics-pretreatment suggest that probiotics is a promising therapeutic agent in the management of diabetic keratopathy.

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

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