July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Low humidity plus anti-cholinergic-induced dry eye skews toward a Th1 response
Author Affiliations & Notes
  • Zhiyuan Yu
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Jehan Alam
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Rodrigo G. de Souza
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Cintia S De Paiva
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Stephen C Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Zhiyuan Yu, None; Jehan Alam, None; Rodrigo de Souza, None; Cintia De Paiva, None; Stephen Pflugfelder, None
  • Footnotes
    Support  NIH/NEY EY11915 (S.C.P.), NIH Core grants EY002520 and EY020799, NIH funding to Cytometry and Cell Sorting Core at Baylor College of Medicine (NIAID P30AI036211, NCI P30CA125123 and NCRR S10RR024574), Biology of Inflammation Center Baylor College of Medicine, an unrestricted grant from Research to Prevent Blindness, New York, NY (S.C.P.), the Oshman Foundation, Houston, TX (S.C.P.), the William Stamps Farish Fund, Houston, TX (S.C.P.), Hamill Foundation, Houston, TX (S.C.P.), Sid W. Richardson Foundation, Ft Worth, TX (S.C.P.).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 275. doi:
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    • Get Citation

      Zhiyuan Yu, Jehan Alam, Rodrigo G. de Souza, Cintia S De Paiva, Stephen C Pflugfelder; Low humidity plus anti-cholinergic-induced dry eye skews toward a Th1 response. Invest. Ophthalmol. Vis. Sci. 2019;60(9):275.

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

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Abstract

Purpose : Mouse dry eye models have been created with low humidity (LH) plus anti-cholinergic suppression of tear secretion or LH alone. We investigated the ocular surface immune response to these different dry eye-inducing conditions, with particular attention to their effects on Th1 (CD4+IFN-γ+) and Th17 (CD4+IL-17A+) polarization.

Methods : 6-to-8 week old C57BL/6J mice were housed under normal humidity and left untreated or subjected to LH or LH and scopolamine SC (LH+Scop) for 1 day (D1) and 10 days (D10), respectively. Populations of Th1 and Th17 cells were analyzed in the cervical lymph nodes (CLNs) by flow cytometry. Expression of Th1 genes (IFN-γ, CXCL10 and Sprr2f, Sprr2g) and Th17 genes (IL-17A, CCL20 and MMP9) in the conjunctiva and cornea was evaluated by real-time PCR.

Results : Compared to naïve mice, greater frequency of Th1 cells at D10 in the LH+Scop group, and elevated frequency of Th17 cells was detected at D10 in LH and LH+Scop groups in the CLNs (P<0.0001). Expression of Th1 genes in the conjunctiva showed IFN-γ unchanged at D1 and significantly higher at D10 in the LH+Scop group (2 fold, P<0.0001). CXCL10 was higher at D10 in the conjunctiva of the LH group compared to LH+Scop (1.9 fold, P<0.001). Sprr2f and Sprr2g, two IFN-γ induced cornified envelope genes, were higher in cornea in LH+Scop compared to LH (Sprr2f: 2.9 vs. 0.45 (D1) and 18.6 vs. 14.3 (D10); Sprr2g: 5 vs. 2.5 fold (D1) and 3 vs. 1.3 fold (D10); respectively, P<0.0001 for both). Expression of IL-17 genes showed early upregulation of IL-17A (2.70 fold, P<0.0001) in the LH group. In the cornea, IL-17A was significantly higher at D1 and and undetected at D10 in both LH and LH+Scop groups (~20 and 5 fold, respectively, P<0.0001 for both). CCL20 peaked at D1 in the cornea (~12 fold) and in the conjunctiva (2.37 fold) in the LH group, while it was significantly elevated in cornea at D1 and D10 in the LH+Scop groups (4.6 and 4.2fold, D1 and D10, respectively, P<0.0001). MMP9 increased 2 fold at 1 day (P <0.0001) only in the LH group.

Conclusions : These findings indicate that different dry eye inducing conditions in mice show a different pattern of T helper immune response. LH+Scop skews toward a Th1 response; whereas LH alone promotes a Th17 biased response. These finding suggest that secreted tear factors suppress Th1 induction and IFN-γ+ expression. They suggest that therapy of aqueous tear deficiency should include agents that suppress Th1.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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