July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Lacrimal gland acinar TRAIL (CD253) expression is essential for inhibiting bone marrow-derived CD45+ inflammatory cell infiltration in dry eye disease
Author Affiliations & Notes
  • Hyung Keun Lee
    Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Yong Woo Ji
    Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Eunyoung Choi
    Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Arum Yeo
    Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Hyung Keun Lee, None; Yong Woo Ji, None; Eunyoung Choi, None; Arum Yeo, None
  • Footnotes
    Support  NRF-2018R1A2B3001110, NRF-2017M3A7B4041798
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 296. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Hyung Keun Lee, Yong Woo Ji, Eunyoung Choi, Arum Yeo; Lacrimal gland acinar TRAIL (CD253) expression is essential for inhibiting bone marrow-derived CD45+ inflammatory cell infiltration in dry eye disease. Invest. Ophthalmol. Vis. Sci. 2019;60(9):296.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The purpose of this study is to investigate the expression levels of death ligands, identify upstream factors that regulate their expression, and determine the functional roles of these factors in the pathogenesis of dry eye (DE) by examining DE-induced LGs, focused especially on cell infiltration.

Methods : C57BL/6 mice and hypoxia-inducible factor (HIF)-1α conditional knockout (CKO) mice were used for DE induction. After DE induction, mice were sacrificed serially and their LGs were collected. Immunohistochemical staining, qPCR, ELISA, and immunoblot assay was performed to determine the level of TRAIL (CD253) and five TRAIL receptors, Fas/FasL, and PD/PDL-1 systems in the DE-induced LGs. Also, acinar cell and CD45+ cell apoptosis were determined with neutralizing TRAIL antibody treatment.

Results : CD45+ and CD11b+ cells were increased in LG from 2 days after DE induction.
Among the death ligands, only TRAIL was up-regulated and synchronized with the cell infiltration period. Surprisingly, the LG acinar, not the infiltrating leukocytes, was the main source of LG TRAIL. After neutralizing expression of TRAIL, leukocyte infiltration and acinar cell death was significantly enhanced in DE-induced LG (p<0.001) in both in vivo and ex vivo experiments. From the study of HIF-1α CKO mouse experiments, TRAIL was not upregulated by DE induction. Furthermore, severe CD45+ cell infiltration and acinar cell apoptosis was confirmed.

Conclusions : DE-induced TRAIL and its receptor system are essential for preventing LG acinar cell apoptosis due to DE-induced leukocyte infiltration and inflammation, and are regulated by the activation of HIF-1α.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×