July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Enhanced orbital adipogenesis in a mouse model of T-cell-mediated autoimmunity, zymosan A-treated SKG mice: Implications for Graves’ ophthalmopathy
Author Affiliations & Notes
  • Dong Hui Lim
    Ophthalmology, Samsung Medical Center, Seoul, Korea (the Republic of)
  • Jaeryung Kim
    Ophthalmology, Samsung Medical Center, Seoul, Korea (the Republic of)
  • Tae-Young Chung
    Ophthalmology, Samsung Medical Center, Seoul, Korea (the Republic of)
  • Ji Sang Han
    Ophthalmology, Myongji Hospital, Goyang-si, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Dong Hui Lim, None; Jaeryung Kim, None; Tae-Young Chung, None; Ji Sang Han, None
  • Footnotes
    Support  NRF-2017R1C1B2075688; Seoul, Korea
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2553. doi:
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      Dong Hui Lim, Jaeryung Kim, Tae-Young Chung, Ji Sang Han; Enhanced orbital adipogenesis in a mouse model of T-cell-mediated autoimmunity, zymosan A-treated SKG mice: Implications for Graves’ ophthalmopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2553.

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

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Abstract

Purpose : Inflammation and remodeling of orbital tissue associated with enhanced adipogenesis commonly occur in Graves’ ophthalmopathy and idiopathic orbital inflammation, however, the underlying mechanisms that link immune cells and adipocytes in orbital inflammation are little known. The primary aim of this study was to elucidate how a genetically determined shift of the T-cell repertoire toward self-reactive T-cells could drive orbital adipogenesis.

Methods : SKG mice (BALB/c mice that harbor the point mutation in ZAP-70) were housed under pathogen–free conditions. To induce T-cell-mediated autoimmune response, zymosan-A (or vehicle in a control) was intraperitoneally injected once at 8 week old. Three months after the injection, orbital magnetic resonance imaging (MRI) and histopathologic studies of the exenterated eyelid and orbit were performed to evaluate inflammation, fibrosis and adipogenesis.

Results : The eyes of SKG mice in response to zymosan displayed proptosis and inflammatory responses as indicated by significant increase in the thickness of lid and meibomian gland, and subepithelial cellular infiltration. The detailed analysis of orbital adipose tissue in zymosan-induced SKG mice showed enhanced orbital adipogenesis with fat browning but no distinct cellular infiltration or fibrosis compared to control. The extraocular muscles in zymosan-induced SKG mice exhibited angulated fibers without swelling indicating atrophic change in muscle. No significant difference was observed in the follicles of thyroid gland between control and zymosan-induced SKG mice.

Conclusions : The orbital adipogenesis was demonstrated in zymosan-induced SKG mice with self T-cell activation. This study allows us to understand the complexity surrounding the pathogenesis of orbital adipogenesis associated with T-cell dysfunction and may provide the therapeutic potential target alternative to steroid and surgical treatment in orbital inflammation disease.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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