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Apoptosis of Ocular Surface Cells in Experimentally Induced Dry Eye
Abstract
PURPOSE: To evaluate to effect of experimental dry eye on ocular surface apoptosis. METHODS: Aqueous tear production and clearance were inhibited by systemic administration of scopolamine and exposure to an air draft for 12 days in 4- to 6-week-old 129SvEv/CD-1 mixed white mice. Eyes and ocular adnexa were excised, cryosectioned, and evaluated for apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemical assay for caspase-3 and poly(ADP-ribose) phosphate (PARP), and examination of nuclear morphologic changes by Hoechst DNA nuclear staining and transmission electron microscopy. RESULTS: The number of TUNEL-positive cells in the mice with induced dry eye was significantly increased compared with control mice in the following ocular regions: central corneal (P < 0.0014), peripheral corneal (P < 0.0001), bulbar conjunctival (P < 0.0021), and tarsal conjunctival (P < 0.0046) epithelia; tarsal conjunctival stroma (P < 0.0274); and lid margin (P < 0.0219, n = 4 in all cases). There were no significant differences observed between treated and control groups in the central corneal, peripheral corneal, or bulbar conjunctival stroma; meibomian glands; skin; retina-choroid; or episcleral regions. Immunohistochemistry for caspase-3 and poly(ADP-ribose) polymerase p85 fragment revealed increased immunoreactivity in regions of increased TUNEL positivity, particularly in the corneal and conjunctival epithelial cells. Ultrastructural morphologic changes consistent with apoptosis were observed in the conjunctival epithelial cells. CONCLUSIONS: Experimentally induced dry eye in mice causes apoptosis of cells in ocular surface tissues including the central and peripheral corneal epithelium, bulbar and tarsal conjunctival epithelia, tarsal conjunctival stroma, and lid margin. Apoptosis may play a key role in the pathogenesis of keratoconjunctivitis sicca and may be a therapeutic target for this condition.
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Cited by
Luo, L., Li, D.-Q., Doshi, A., Farley, W., Corrales, R. M., & Pflugfelder, S. C. (2004) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.03-1145 · Cited by 595
Self-citationDry Eye–Induced Conjunctival Epithelial Squamous Metaplasia Is Modulated by Interferon-γ
De Paiva, C. S., Villarreal, A. L., Corrales, R. M., Rahman, H. T., Chang, V. Y., Farley, W. J., Stern, M. E., Niederkorn, J. Y., Li, D.-Q., & Pflugfelder, S. C. (2007) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.07-0069 · Cited by 320
Self-citationDeinema, L. A., Vingrys, A. J., Wong, C. Y., Jackson, D. C., Chinnery, H. R., & Downie, L. E. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2016.09.023 · Cited by 160
Tseng, C.-L., Hung, Y.-J., Chen, Z.-Y., Fang, H.-W., & Chen, K.-H. (2016) · PLOS ONE · doi:10.1371/journal.pone.0157982 · Cited by 53
Therapeutic Effect of MK2 Inhibitor on Experimental Murine Dry Eye
Wu, Y., Bu, J., Yang, Y., Lin, X., Cai, X., Huang, C., Zheng, X., Ouyang, W., Li, W., Zhang, X., et al. (2017) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.17-22240 · Cited by 12
Metadata
- Authors
- Yeh, S., Song, X. J., Farley, W., Li, D.-Q., Stern, M. E., & Pflugfelder, S. C.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2003-01-01
- Volume
- 44
- Issue
- 1
- Pages
- 124
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2075995435
- Cited by
- 308
- References
- 0
- FWCI
- 10.88
- Type
- journal article
- Language
- en
- Open access
- closed
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