The association between altered intestinal microbiome, impaired systemic and ocular surface immunity, and impaired wound healing response after corneal alkaline-chemical injury in diabetic mice

被引:6
|
作者
Bu, Yashan [1 ]
Shih, Kendrick Co [1 ]
Wong, Ho Lam [1 ]
Kwok, Sum Sum [1 ]
Lo, Amy Cheuk-Yin [1 ]
Chan, Joseph Yau-Kei [1 ]
Ng, Alex Lap-Ki [1 ]
Chan, Tommy Chung-Yan [2 ]
Jhanji, Vishal [3 ]
Tong, Louis [4 ,5 ]
机构
[1] Univ Hong Kong, Li Ka Shing Fac Med, Dept Ophthalmol, Pokfulam, Hong Kong, Peoples R China
[2] Hong Kong Sanat & Hosp, Dept Ophthalmol, Hong Kong, Peoples R China
[3] Univ Pittsburgh, Dept Ophthalmol, Med Ctr, Pittsburgh, PA USA
[4] Singapore Natl Eye Ctr, Cornea & External Eye Dis Serv, Singapore, Singapore
[5] Singapore Eye Res Inst, Ocular Surface Res Grp, Singapore, Singapore
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
关键词
intestinal microbiome; diabetes; corneal wound healing; alkaline chemical injury; T-cell mediated immunity; ocular surface; ENDOTHELIAL GROWTH-FACTOR; AKKERMANSIA-MUCINIPHILA; GUT MICROBIOTA; POPULATION; DIET; EYE;
D O I
10.3389/fimmu.2023.1063069
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
PurposeWe aim to investigate the effect of sustained hyperglycemia on corneal epithelial wound healing, ocular surface and systemic immune response, and microbiome indices in diabetic mice compared to controls after alkaline chemical injury of the eye. MethodsCorneal alkaline injury was induced in the right eye of Ins2(Akita) (Akita) mice and wild-type mice. The groups were observed at baseline and subsequently days 0, 3, and 7 after injury. Corneal re-epithelialization was observed under slit lamp with fluorescein staining using a cobalt blue light filter. Enucleated cornea specimens were compared at baseline and after injury for changes in cornea thickness under hematoxylin and eosin staining. Tear cytokine and growth factor levels were measured using protein microarray assay and compared between groups and time points. Flow cytometry was conducted on peripheral blood and ocular surface samples to determine CD3+CD4+ cell count. Fecal samples were collected, and gut microbiota composition and diversity pattern were measured using shotgun sequencing. ResultsAkita mice had significantly delayed corneal wound healing compared to controls. This was associated with a reduction in tear levels of vascular endothelial growth factor A, angiopoietin 2, and insulin growth factor 1 on days 0, 3, and 7 after injury. Furthermore, there was a distinct lack of upregulation of peripheral blood and ocular surface CD3+CD4+ cell counts in response to injury in Akita mice compared to controls. This was associated with a reduction in intestinal microbiome diversity indices in Akita mice compared to controls after injury. Specifically, there was a lower abundance of Firmicutes bacterium M10-2 in Akita mice compared to controls after injury. ConclusionIn diabetic mice, impaired cornea wound healing was associated with an inability to mount systemic and local immune response to ocular chemical injury. Baseline and post-injury differences in intestinal microbial diversity and abundance patterns between diabetic mice and controls may potentially play a role in this altered response.
引用
收藏
页数:14
相关论文
共 4 条
  • [1] Sustained hyperglycemia impairs corneal re-epithelialization after alkaline injury through modulation of the ocular surface, systemic Immunity and intestinal microbiome
    Bu, Yashan
    Chan, Yau
    Lo, Amy
    Shih, Kendrick
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2021, 62 (08)
  • [2] Deciphering the Transformed bacterial ocular surface microbiome in diabetic mice and its Consequential influence on corneal wound healing restoration
    Wang, Huifeng
    Xue, Junfa
    Song, Yi
    Li, Dewei
    Wei, Chao
    Wan, Luqin
    EXPERIMENTAL EYE RESEARCH, 2025, 255
  • [3] Probiotics pretreatment attenuates impaired corneal re-epithelialization in diabetic mice through amelioration of T cell immunity and remodulation of the intestinal microbiome
    Bu, Yashan
    Xu, Sheng
    Chan, Yau Kei
    Lo, Amy C. Y.
    Ho, Joshua Wing-Kei
    Shih, Kendrick Co
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2022, 63 (07)
  • [4] The Effect of Hyperglycemia on Gut Microbial diversity, Ocular Surface Inflammation and Corneal Re-epithelialization after Alkaline Chemical Injury in Mice
    Bu, Yashan
    Shih, Kendrick Co
    Lo, Amy C. Y.
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2019, 60 (09)