May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Effects of IFN and Cyclosporin A (CsA) on Tear Production in a Mouse Model of Keratoconjunctivitis Sicca (KCS)
Author Affiliations & Notes
  • M.E. Stern
    Biological Sciences, Allergan Inc, Irvine, CA, United States
  • K.F. Siemasko
    Biological Sciences, Allergan Inc, Irvine, CA, United States
  • J. Gao
    Biological Sciences, Allergan Inc, Irvine, CA, United States
  • J.Y. Niederkorn
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, United States
  • M. Calonge
    Laboratorio Canga-Arqueros, IOBA, University of Valladolid, Valladolid, Spain
  • S.C. Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, TX, United States
  • Footnotes
    Commercial Relationships  M.E. Stern, Allergan, Inc. E; K.F. Siemasko, Allegan, Inc. E; J. Gao, Allergan, Inc. E; J.Y. Niederkorn, Allergan, Inc. C; M. Calonge, Allergan, Inc. C; S.C. Pflugfelder, Allergan, Inc. C.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 2531. doi:
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      M.E. Stern, K.F. Siemasko, J. Gao, J.Y. Niederkorn, M. Calonge, S.C. Pflugfelder; Effects of IFN and Cyclosporin A (CsA) on Tear Production in a Mouse Model of Keratoconjunctivitis Sicca (KCS) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2531.

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

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Abstract

Abstract: : Purpose: To determine the role of IFNγ in a mouse model of keratoconjunctivitis sicca (KCS). Methods: Female C57BL6 wild type mice or C57BL6 IFNγ knockout mice received injections of 0.5 mg scopolamine (subQ) TID for 4 consecutive days. Mice were placed in a blower hood in the presence of a continuous air draft produced by a fan for 8 hours a day. This treatment increases corneal fluorescein permeability, reduce conjunctival goblet cell number, and enhance conjunctival epithelial proliferation, all characteristics of human KCS (IOVS 2002;43, 632-638). For studies analyzing the effects of cyclosporin A (CsA), wild type C57BL6 female mice were treated with either CsA (10 µl TID per eye) or vehicle (10 µl TID per eye) for 7 days prior to and continuing through a 4 day blower treatment. Zone quick cotton threads were placed in the lateral canthus of the right eye for 30 seconds to measure aqueous tear production every morning and evening. Results: The average tear production before treatment in wild type and IFNγ knockout mice was 4.5 and 3.5 mm, respectively. Treatment of all groups with scopolamine and desiccating environmental stress resulted in a significant decrease in tear production to 1.2 mm or less after 8 hours. The ability of tear production to rebound overnight to pretreatment levels in wild type mice decreased over the 4 day time course to an average morning tear production reading of 0.8 mm on day 4 (a net decrease of 3.7 mm or 82%). In contrast, IFNγ knockout mice went from a tear production average of 3.5 mm before treatment to day 4 morning tear production average of 2.5mm (a net decrease of 1 mm or 29%). CsA treated wild type mice had a striking rebound of tear production overnight to 4.5 mm. Conclusions: Inflammation (primarily Th1 mediated) is a major component of KCS. We have demonstrated in both CsA treated wild type mice and IFNγ knockout mice (unable to generate a Th1 response) that prevention of Th1 inflammatory responses preserves normal tear secretion and mitigates the pathological sequelae of dry eye disease. CsA prevention of progressive inflammation-based reduction of lacrimal secretion (as seen in wild type mice) is indicative of its anti-inflammatory properties.

Keywords: inflammation • conjunctiva • lacrimal gland 
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