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Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis.

Publication ,  Journal Article
Chen, Y; Chauhan, SK; Lee, HS; Stevenson, W; Schaumburg, CS; Sadrai, Z; Saban, DR; Kodati, S; Stern, ME; Dana, R
Published in: Invest Ophthalmol Vis Sci
April 3, 2013

PURPOSE: A majority of experimental data on dry eye disease (DED) immunopathogenesis have been derived from a murine model of DED that combines desiccating environmental stress with systemic muscarinic acetylcholine receptor (mAChR) inhibition. However, to our knowledge the effects of pharmacologic mAChR blockade on the pathogenesis of experimental DED have not been evaluated systemically. The purpose of our study was to investigate the differential effects of desiccating environmental stress and mAChR inhibition on the pathogenesis of DED. METHODS: DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled-environment chamber or to systemic scopolamine, or by performing extraorbital lacrimal gland excision. Clinical disease was assessed using corneal fluorescein staining (CFS) and the cotton thread test (CTT). Corneal CD11b(+) and conjunctival CD3(+) T-cell infiltration were evaluated by flow cytometry. T-cells from draining cervical lymph nodes (CLN) and distant inguinal lymph nodes (ILN) were analyzed for Th1, Th2, Th17, and Treg responses by flow cytometry and ELISA. RESULTS: Desiccating environmental stress and systemic mAChR blockade induced similar clinical signs of DED. However, desiccating environmental stress imparted higher conjunctival CD3(+) T-cell infiltration, and greater Th17-cell activity and Treg dysfunction than mAChR blockade, while mAChR blockade decreased tear secretion to a greater extent than desiccating environmental stress. Systemic mAChR blockade attenuated Th17 activity and enhanced Th2 and Treg responses without affecting Th1 activity. CONCLUSIONS: In vivo inhibition of mAChRs variably affects CD4(+) T-cell subsets, and desiccating environmental stress and systemic mAChR blockade induce DED through different primary pathogenic mechanisms.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

April 3, 2013

Volume

54

Issue

4

Start / End Page

2457 / 2464

Location

United States

Related Subject Headings

  • Th2 Cells
  • Th17 Cells
  • Th1 Cells
  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Stress, Physiological
  • Scopolamine
  • Receptors, Muscarinic
  • Ophthalmology & Optometry
  • Muscarinic Antagonists
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, Y., Chauhan, S. K., Lee, H. S., Stevenson, W., Schaumburg, C. S., Sadrai, Z., … Dana, R. (2013). Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis. Invest Ophthalmol Vis Sci, 54(4), 2457–2464. https://doi.org/10.1167/iovs.12-11121
Chen, Yihe, Sunil K. Chauhan, Hyun Soo Lee, William Stevenson, Chris S. Schaumburg, Zahra Sadrai, Daniel R. Saban, Shilpa Kodati, Michael E. Stern, and Reza Dana. “Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis.Invest Ophthalmol Vis Sci 54, no. 4 (April 3, 2013): 2457–64. https://doi.org/10.1167/iovs.12-11121.
Chen Y, Chauhan SK, Lee HS, Stevenson W, Schaumburg CS, Sadrai Z, et al. Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis. Invest Ophthalmol Vis Sci. 2013 Apr 3;54(4):2457–64.
Chen, Yihe, et al. “Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis.Invest Ophthalmol Vis Sci, vol. 54, no. 4, Apr. 2013, pp. 2457–64. Pubmed, doi:10.1167/iovs.12-11121.
Chen Y, Chauhan SK, Lee HS, Stevenson W, Schaumburg CS, Sadrai Z, Saban DR, Kodati S, Stern ME, Dana R. Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis. Invest Ophthalmol Vis Sci. 2013 Apr 3;54(4):2457–2464.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

April 3, 2013

Volume

54

Issue

4

Start / End Page

2457 / 2464

Location

United States

Related Subject Headings

  • Th2 Cells
  • Th17 Cells
  • Th1 Cells
  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Stress, Physiological
  • Scopolamine
  • Receptors, Muscarinic
  • Ophthalmology & Optometry
  • Muscarinic Antagonists