May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Ocular Surface Plays an Antigenic Role in the Initiation of a Mouse Model of Dry Eye Disease
Author Affiliations & Notes
  • M. E. Stern
    Biological Sciences, Allergan, Inc, Irvine, California
  • S. C. Pflugfelder
    Cullen Eye Institute, Baylor College of Medicine, Houston, Texas
  • K. F. Siemasko
    Biological Sciences, Allergan, Inc, Irvine, California
  • J. Gao
    Biological Sciences, Allergan, Inc, Irvine, California
  • V. L. Calder
    Institute of Ophthalmology, University College London, London, United Kingdom
  • M. Calonge
    IOBA, University of Valladolid, Valladolid, Spain
  • J. Y. Niederkorn
    Ophthalmology, UT SW-Med Center, Dallas, Texas
  • Footnotes
    Commercial Relationships  M.E. Stern, Allergan, Inc., E; S.C. Pflugfelder, Allergan, Inc., C; K.F. Siemasko, Allergan, Inc., E; J. Gao, Allergan, Inc., E; V.L. Calder, Allergan, Inc., C; M. Calonge, Allergan, Inc., C; J.Y. Niederkorn, Allergan, Inc., C.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 188. doi:https://doi.org/
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      M. E. Stern, S. C. Pflugfelder, K. F. Siemasko, J. Gao, V. L. Calder, M. Calonge, J. Y. Niederkorn; The Ocular Surface Plays an Antigenic Role in the Initiation of a Mouse Model of Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2008;49(13):188. doi: https://doi.org/.

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

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Abstract

Purpose: : To determine if immunization with conjunctival or corneal epithelial cell suspensions from mice exposed to a dry, desiccating environment will induce pathogenic CD4+ T cells that can produce dry eye disease when adoptively transferred to athymic mice.

Methods: : C57BL/6 wild type (WT) female mice were exposed to a desiccating environmental stress (DS; subcutaneous scopolamine injections (0.5 mg/0.2 ml) TID, humidity <40%, and air flow by fans across wire meshed screened cages) for 10 days. Anti-CD25 antibody treated C57BL/6 WT mice were immunized by hind footpad injection in the presence of CFA with control or DS conjunctiva (1 X 106) or cornea (7 X 105) epithelial cells. After 5 days, 5 X 106 spleen and cervical lymph node CD4+ T cells from immunized mice were injected IP into syngeneic T-cell deficient athymic recipients kept under non-stressed conditions. Recipient mice were sacrificed four days later and tissues were collected. Immunized and recipient tears were collected for detection of inflammatory cytokines using Luminex technology.

Results: : The immunized mice had a minimal response as evaluated by tear production, histology, and tear cytokine levels. However, CD4+ cells from mice immunized with DS cornea epithelial cells had a statistically significant increase in IL-12, IL-1β and TNF-α tear levels as compared to mice receiving the control cornea CD4+ cells. A statistically significant (*P=0.025) cellular infiltration into conjunctiva of recipient mice receiving CD4+ cells from mice immunized with DS conjunctiva epithelial cells was detected. There was significant cellular infiltration of both mononuclear cells (*P=0.014) and neutrophils (*P=0.001) into the conjunctiva of athymic recipient mice receiving CD4+ T cells from immunized mice that were injected with DS cornea cells. Adoptive transfer of CD4+ cells from immunized mice receiving control conjunctiva or cornea epithelial cells did not induce high cytokine tear levels in recipient mice.

Conclusions: : The results from the athymic recipient mice confirm that DS conjunctiva and cornea epithelial cells contain an antigenic determinant which is capable of generating pathogenic CD4+ T cells. Conjunctival and corneal epithelial cells exposed to a dry, desiccating environment have the capacity to initiate a CD4+ mediated immune response that is transferable.

Keywords: cornea: tears/tear film/dry eye • inflammation • cornea: epithelium 
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