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