April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
The Role of sPLA2-IIa in the Experimental Dry Eye Mouse Model
Author Affiliations & Notes
  • Y. Wei
    Ophthalmology, Mount Sinai School of Medicine, New York, New York
  • S. P. Epstein
    Ophthalmology, Mount Sinai School of Medicine, New York, New York
  • S. Fukuoka
    Ophthalmology, Mount Sinai School of Medicine, New York, New York
  • P. A. Asbell
    Ophthalmology, Mount Sinai School of Medicine, New York, New York
  • Footnotes
    Commercial Relationships  Y. Wei, None; S.P. Epstein, None; S. Fukuoka, None; P.A. Asbell, None.
  • Footnotes
    Support  This study was supported in part by the Martin and Toni Sosnoff Foundation.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4314. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Y. Wei, S. P. Epstein, S. Fukuoka, P. A. Asbell; The Role of sPLA2-IIa in the Experimental Dry Eye Mouse Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4314.

      Download citation file:

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

  • Supplements

Purpose: : Group II secretory phospholipase sPLA-IIa has been shown an inflammatory mediator in human dry eye disease. Studies utilizing a murine model have confirmed that mice with scopolamine-induced dry eye develop T-cell dominant ocular surface immune responses. This study analyzed the change in expression of sPLA2-IIa and inflammatory cytokines in this experimental dry eye mouse model.

Methods: : Forty-five 6-8 week old female BALB/c mice, 5 mice/group, were injected with scopolamine, 2.5 mg/day and placed in specially designed environmentally controlled cages with daytime fan-circulated air for 5-10 days. Control mice received no scopolamine and no fan. Tear samples at Days 1, 5, 10 were collected for quantification of tear production by pheno-red thread and tear inflammatory cytokine quantification by MILLIPLEX cytokine panel. Biopsy samples of cornea, conjunctiva and lacrimal gland were analyzed for inflammation and goblet cell density by standard H&E and PAS staining. sPLA2-IIa protein expression was assayed by immunofluorescence (IF), immunohistochemistry(IHC) and qRT-PCR.

Results: : Tear thread measurement showed a significant decrease in tear production at Day 5 of scopolamine injection (treated: 2.17 ± 0.75 mm, control: 7.08 ± 3.14 mm, p<0.0001), a deficiency maintained through Day 10 (treated: 2.44 ± 1.08 mm, control: 7.20 ± 3.08 mm, p<0.0001). Corneal staining with fluorescein confirmed heavy staining only in treated eyes, indicating ocular surface compromise. Compared to non-treated controls, the goblet cell densities in the conjunctivae of scopolamine-treated mice were significantly reduced (treated: 76.3 ± 35.2, control: 142.7 ± 18.9, p<0.001), while inflammatory cell densities increased. Multiple inflammatory cytokine changes were detected, especially Th2-type, in agreement with others. An increase in expression of sPLA2-IIa in both goblet cells and conjunctiva epithelia cells was noted by ICH and IF. mRNA expression of sPLA2-IIa was found to increase in only conjunctival epithelial cells, no changes were found in cornea epithelia cells or lacrimal gland, consistent with reports in human corneal epithelium.

Conclusions: : Our results indicate scopolamine-induced tear deficiency not only triggers Th-2-dominant ocular surface inflammation, but also promotes expression of sPLA2-IIa, suggesting sPLA2-IIa is involved in the immune modulation of conjunctival epithelium, especially inflammatory responses. Studies elucidating the role(s) and mechanism of sPLA2-IIa in ocular surface inflammation, such as dry eye diseases, may provide new therapeutic strategies to treat these diseases.

Keywords: cornea: tears/tear film/dry eye • inflammation • conjunctiva 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.