April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Autoantibodies Contribute to the Immunopathogenesis of Dry Eye in a Mouse Model of Autoimmune Lacrimal Keratoconjunctivitis
Author Affiliations & Notes
  • Michael E. Stern
    Biological Sciences,
    Allergan, Inc, Irvine, California
  • Christopher S. Schaumburg
    Biological Sciences,
    Allergan, Inc, Irvine, California
  • Karyn F. Siemasko
    Biological Sciences,
    Allergan, Inc, Irvine, California
  • Jianping Gao
    Biological Sci (RD3-2C),
    Allergan, Inc, Irvine, California
  • Larry A. Wheeler
    Biological Sciences,
    Allergan, Inc, Irvine, California
  • Margarita Calonge
    Ocular Surface Group, IOBA-University Of Valladolid, Valladolid, Spain
  • Virginia L. Calder
    Ocular Biology & Therapeutics, UCL Institute of Ophthalmology, London, United Kingdom
  • Jerry Y. Niederkorn
    Ophthalmology, Univ Texas Southwestern Med Ctr, Dallas, Texas
  • Stephen C. Pflugfelder
    Ophthal-Ocular Surf Ctr, Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  Michael E. Stern, Allergan, Inc. (E); Christopher S. Schaumburg, Allergan, Inc. (E); Karyn F. Siemasko, Allergan, Inc. (E); Jianping Gao, Allrgan, Inc. (E); Larry A. Wheeler, Allergan, Inc. (E); Margarita Calonge, Allergan, Inc. (C); Virginia L. Calder, Allergan, Inc. (C); Jerry Y. Niederkorn, Allergan, Inc. (C); Stephen C. Pflugfelder, Allergan, Inc. (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1204. doi:
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      Michael E. Stern, Christopher S. Schaumburg, Karyn F. Siemasko, Jianping Gao, Larry A. Wheeler, Margarita Calonge, Virginia L. Calder, Jerry Y. Niederkorn, Stephen C. Pflugfelder; Autoantibodies Contribute to the Immunopathogenesis of Dry Eye in a Mouse Model of Autoimmune Lacrimal Keratoconjunctivitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1204.

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Abstract

Purpose: : To evaluate the functional role of B cell-derived autoantibodies during the immunopathogenesis of experimental Dry Eye.

Methods: : We previously reported that passive transfer of Dry Eye-specific serum containing autoantibodies, but not B cells alone, induces ocular surface inflammation. To further determine if autoantibodies contribute to disease, experimental Dry Eye was induced by exposing female C57BL/6 wild-type (WT) mice or hen egg lysozyme (HEL) B cell receptor (BCR) transgenic (Tg) mice to desiccating stress (DS: subcutaneous scopolamine (0.5 mg/0.2ml) TID, humidity <40%, and sustained airflow) for 3 weeks. Purified IgG was isolated from mice with Dry Eye or controls and passively transferred to T cell-deficient nude recipient mice, which were subsequently evaluated for ocular surface inflammation 3 days post-transfer.

Results: : By 3 weeks of DS, mice showed elevated titers of serum IgG; passive transfer of purified IgG from DS mice resulted in a significant (p=0.02) decrease in tear production (60.9±10.0% of baseline) compared to recipients of IgG purified from control serum (143.2±29.4% of baseline) that was associated with elevated tear proinflammatory cytokine levels. Marked inflammatory cell infiltration was also observed within the ocular surface tissues of nude recipient mice receiving DS-IgG, and correlated with damage to ocular surface tissues assessed by a significant (p=0.003) decrease in Goblet cell numbers within the conjunctiva of recipients of DS-IgG (49.6±7.6) compared recipients of control IgG (78.4±4.3) or untreated nude mice (86.3±7.9). By contrast, serum from HEL BCR Tg mice exposed to DS was not sufficient to induce disease; however, CD4+ T cells isolated from HEL BCR Tg mice maintained the capacity to transfer Dry Eye disease.

Conclusions: : These data demonstrate that autoantibodies from B cell-derived plasma cells may contribute to the predominantly T cell-mediated immunopathogenesis of Dry Eye disease.

Keywords: inflammation • cornea: tears/tear film/dry eye • antigen presentation/processing 
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