June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Multimodal Evaluation of Immune-Vascular Interaction of Experimental Autoimmune Uveitis
Author Affiliations & Notes
  • Jee Myung Yang
    Ophthalmology, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of)
    Ophthalmology, Dongguk University Ilsan Hospital, Goyang, Gyeonggi-do, Korea (the Republic of)
  • Jehwi Jeon
    Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Daejeon, Korea (the Republic of)
  • Bora Kim
    Ophthalmology, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of)
  • Junyeop Lee
    Ophthalmology, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of)
  • Wang-Yuhl Oh
    Graduate School of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Daejeon, Korea (the Republic of)
  • Seung Won Lee
    Department of Data Science, Sejong University College of Software Convergence, Seoul, Korea (the Republic of)
    Sungkyunkwan University School of Medicine, Suwon, Korea (the Republic of)
  • Akiyoshi Uemura
    Department of Retinal Vascular Biology, Nagoya Shiritsu Daigaku Daigakuin Igaku Kenkyuka Igakubu, Nagoya, Aichi, Japan
  • Pilhan Kim
    Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Daejeon, Korea (the Republic of)
  • Joo Yong Lee
    Ophthalmology, Asan Medical Center, Songpa-gu, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Jee Myung Yang None; Jehwi Jeon None; Bora Kim None; Junyeop Lee None; Wang-Yuhl Oh None; Seung Won Lee None; Akiyoshi Uemura None; Pilhan Kim None; Joo Yong Lee None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4095 – F0059. doi:
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      Jee Myung Yang, Jehwi Jeon, Bora Kim, Junyeop Lee, Wang-Yuhl Oh, Seung Won Lee, Akiyoshi Uemura, Pilhan Kim, Joo Yong Lee; Multimodal Evaluation of Immune-Vascular Interaction of Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4095 – F0059.

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

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Abstract

Purpose : To characterize the vascular phenotypes of an experimental autoimmune retinal uveitis (EAU) model induced by interphotoreceptor retinoid-binding protein (IRBP) using multimodal imaging techniques.

Methods : We systemically administered IRBP or vehicle to adult C57BL/6 mice. Fundus photography, optical coherence tomography (OCT), in vivo live confocal imaging using different tracers, blood flow analysis by OCT angiography (OCTA), and electroretinogram (ERG) were performed after IRBP immunization. Hematoxylin and eosin and immunofluorescent staining were performed to characterize the immune reaction and vascular permeability. Cx3cr1-GFP mice (microglia-reporter mouse) and LysM-GFP mice (neutrophil-reporter mouse) were used for immune cell phenotyping.

Results : EAU mice exhibited perivascular inflammation, vitritis, and superficial retinal inflammation on fundus photography and OCT. H&E revealed immune cell infiltration in the perivascular area of the retina and choroid accompanied by a significant degree of peri-vasculitis that subsequently damaged the photoreceptors 3 weeks post-immunization. Immunofluorescent staining showed subsequent transcytosis induction after local microglial activation followed by neutrophil recruitment at the perivascular area. Transcytosis in the superficial and deep vascular areas was improved by suppressing immune cells (anti-Ly6C- induced neutrophil inhibition and minocycline-induced microglial inhibition). Intravital in vivo confocal imaging showed signs of neutrophil infiltration and obstructive vasculitis with perivascular leakage 3 weeks post-immunization. OCTA revealed a significant decrease in vascular flow in the deep capillary layer of the retina. Function analysis showed that scotopic responses were intact in 2 weeks; however, normal photopic and scotopic responses were hardly detected in EAU mice 3 weeks post-immunization.

Conclusions : Our data suggest that inflammatory cell activation and subsequent transcytosis induction in endothelial cells might be a major pathogenic factor for vascular leakage in uveitis, bring new insights into the pathophysiology of retinal vasculitis in non-infectious uveitis.

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

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