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Kinetics of Corneal Antigen Presenting Cells in Experimental Dry Eye Disease
  1. Hyun Soo Lee1,2,
  2. Afsaneh Amouzegar1,
  3. Reza Dana1
  1. 1 Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute/Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
  2. 2 Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  1. Correspondence to Dr Reza Dana; reza_dana{at}meei.harvard.edu

Abstract

Objective To evaluate dry eye disease (DED)-induced alterations in subsets of corneal antigen presenting cells (APCs) in a mouse model of experimental DED.

Methods and Analysis Seven to 8-week-old female C57BL/6 mice were housed in a controlled environment chamber and were treated with subcutaneous scopolamine to induce DED. Normal mice were used as controls. The frequencies of different subsets of dendritic cells (DCs) and macrophages in the cornea were evaluated using immunohistochemistry and flow cytometry at days 2, 7 and 14 after DED induction. Real-time PCR was used to assess the functional phenotype of macrophages in the cornea of DED mice.

Results Our results demonstrated significant corneal infiltration of CD11b+ and CD11c+ cells on days 7 and 14. Further analysis of different DC subsets revealed non-significant changes in the frequencies of total CD11b+CD11c+ cells at different time points. However, frequencies of CD11c+CD11b- DCs, CD11c+ Langerin (CD207)+ DCs and macrophages were significantly increased on both days 7 and 14 after DED induction. Real-time PCR data demonstrated increased expression of M1 macrophage markers, iNOS and TNF-α, and reduced expression of M2 macrophage markers, Arg1 and IL-10, by corneal F4/80+ macrophages at day 7.

Conclusion Although the frequencies of total CD11b+CD11c+ cells do not significantly change in the course of DED, CD11c+CD11b- DCs and Langerin+ DCs do show a significant increase. Interestingly, macrophages exhibit a predominant inflammatory M1 phenotype and suppressed anti-inflammatory M2 phenotype early after induction of DED, which are restored to near baseline levels in later stages of the disease.

  • cornea
  • immunology
  • inflammation

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Acknowledgements The authors would like to thank Dr. Daniel R. Saban (PhD) for his technical help with flow cytometry and critical review of the manuscript.

  • Contributors HSL performed the experiments, analyzed the data and wrote the paper. AA analyzed the data and wrote the paper. RD designed the study, analyzed the data and approved the final version of the manuscript.

  • Funding This study was supported by the National Institutes of Health/National Eye Institute Grant R01EY20889 (RD) and the National Eye Institute Core grant P30EY003790 (Schepens Eye Research Institute).

  • Competing interests None declared.

  • Patient consent Study does not involve human subjects.

  • Provenance and peer review Commissioned; externally peer reviewed.