April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
IFN-Gamma Modulates Dry Eye-Induced Apoptosis on Ocular Surface
Author Affiliations & Notes
  • X. Zhang
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • W. Chen
    Sch of Ophthal & Optometry, Wenzhou Medical College, Wenzhou, China
  • C. S. De Paiva
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • D.-Q. Li
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • S. C. Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  X. Zhang, None; W. Chen, None; C.S. De Paiva, None; D.-Q. Li, None; S.C. Pflugfelder, None.
  • Footnotes
    Support  NIH grant EY11915 (SCP), Research to Prevent Blindness, Oshman Foundation, William Stamps Farish Fund, Allergan.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1560. doi:
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      X. Zhang, W. Chen, C. S. De Paiva, D.-Q. Li, S. C. Pflugfelder; IFN-Gamma Modulates Dry Eye-Induced Apoptosis on Ocular Surface. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1560.

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

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Purpose: : Ocular surface apoptosis can be triggered by multiple cytokines induced by inflammatory responses in dry eye. The purpose of this study was to investigate the role of interferon (IFN)- γ in the pathological apoptosis of ocular surface in dry eye.

Methods: : Experimental dry eye (EDE) was created by subjecting C57BL/6 and IFN-γ-knockout (KO) mice to desiccating environmental stress for 5 days. A separate group mice of both strains also received subconjuctival injection of exogenous IFN-γ or vehicle control at days 0, +2 and +4 after desiccating treatment. Eyes and ocular adnexa were excised, cryosectioned, and evaluated for apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay and immunofluorescent assay for active caspase-3 (Ac-caspase-3). The apoptosis of goblet cells was assessed by MUC5AC and TUNEL double staining.

Results: : Significant increased of Ac-caspase-3 immunostaining was noted in corneal and conjunctival epithelia in C57B/6 mice compared to IFN-γKO mice (P<0.01for cornea and conjunctiva). TUNEL assay confirmed the results of Ac-caspase-3 immunostaining. The number of apoptotic conjunctival epithelial cells was greatest in goblet cell area and was accompanied by an increased number of apoptotic goblet cells in C57B/6 group and C57B/6- IFN-γ injected group compared to IFN-γKO group and BSA-injected group (P<0.05for each comparison). Reconstitution of IFN-γ in IFN-γKO mice after EDE produced similar changes to the C57B/6 wide-type mice.

Conclusions: : IFN-γ plays a pivotal role in promoting apoptosis of ocular surface in dry eye by increasing the level of Ac-caspase-3.

Keywords: conjunctiva • cornea: epithelium • cytokines/chemokines 

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