June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Evidence for IL-2 signaling in corneal epithelium
Author Affiliations & Notes
  • Sonali Pal Ghosh
    Anatomy and Cell Biology, GWU Medical School, Washington DC, District of Columbia, United States
  • Zhiyuan Yu
    Ophthalmology, Ocular Surface Center, Houston, Texas, United States
  • Yashaswini Kelegere
    Ophthalmology, Ocular Surface Center, Houston, Texas, United States
  • Ghasem Yazdanpanah
    Ophthalmology, Ocular Surface Center, Houston, Texas, United States
  • Gauri Tadvalkar
    Anatomy and Cell Biology, GWU Medical School, Washington DC, District of Columbia, United States
  • Winston Kao
    Ophthalmology, College of Medicine University of Cincinnati, Cincinnati, Ohio, United States
  • Vivien Jane Coulson-Thomas
    College of Optometry, University of Houston, Houston, Texas, United States
  • Mary Ann Stepp
    Anatomy and Cell Biology, GWU Medical School, Washington DC, District of Columbia, United States
  • Cintia S De Paiva
    Ophthalmology, Ocular Surface Center, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Sonali Ghosh None; Zhiyuan Yu None; Yashaswini Kelegere None; Ghasem Yazdanpanah None; Gauri Tadvalkar None; Winston Kao None; Vivien Coulson-Thomas None; Mary Ann Stepp None; Cintia De Paiva Yuyu Pharma, Roche and Allysta., Code F (Financial Support)
  • Footnotes
    Support  This work was supported by the NIH/NEI EY026893 & EY030447 (CSDP), EY08512 (MAS), NIH EY-002520 (Core Grant for Vision Research Department of Ophthalmology), Research to Prevent Blindness (Dept. of Ophthalmology), The Hamill Foundation, The Sid Richardson Foundation.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3246 – A0281. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Sonali Pal Ghosh, Zhiyuan Yu, Yashaswini Kelegere, Ghasem Yazdanpanah, Gauri Tadvalkar, Winston Kao, Vivien Jane Coulson-Thomas, Mary Ann Stepp, Cintia S De Paiva; Evidence for IL-2 signaling in corneal epithelium. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3246 – A0281.

      Download citation file:

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

  • Supplements

Purpose : IL-2 signals through its heterotrimeric receptor (IL-2R) consisting of the α (CD25), β, and g chains. We previously reported the gene expression of all three IL-2R chains in the cornea. Our purpose is to investigate the existence of corneal epithelial IL-2 signaling.

Methods : Eyes and adnexa of female C57BL/6 mice were collected, snap-frozen in liquid nitrogen. Cryosections were stained with antibodies anti-CD25, IL-2Rβ, and IL-2Rg and digital images were acquired with laser scanning confocal microscopy. Immortalized human corneal epithelial cells were grown for 24 h in media with increasing concentrations of IL-2 (0, 50, 125, 250, 500, or 1000 IU),fixed, and stained with an antibody against Ki67. The number of Ki67+ cells was quantified within 6 non-overlapping fields per well; 3 wells were assessed per variable; the study was repeated twice. Tet-On Krt12rtTA (Keratin 12-reverse tetracycline-trans-activator knock-in), tet-O-Cre, and CD25flox lines were mated to create ternary Krt12rtTA/rtTA/tet-O-Cre/CD25flox/flox (K12r/r/TC/CD25f/f) in which CD25f/f was ablated in corneal epithelium upon doxycycline induction hereafter named CD25D/DCEpi. K12r/r/TC/CD25f/f without Dox induction and binary K12r/r/CD25f/f with dox induction serve as controls. Both male and female experimental mice were subjected to the corneal barrier function assay at eight weeks of age using Oregon-Green-Dextran (OGD) dye (n = 8-16/condition/sex).

Results : In C57BL/6, CD25, IL-2R-β, and IL-2R-g chains were present in the corneal epithelium. There was a significant increase in Ki67+ cells/field at IL-2 doses of 125 and 250 U/mL followed by a plateau at higher concentrations (P <0.05 and P<0.01, respectively) in human corneal epithelial cells in vitro. A significant increase in corneal OGD levels (indicating corneal barrier disruption) was observed only in the female doxycycline-fed CD25D/DCEpi mice compared to the doxycycline-fed binary K12r/r/CD25f/f mice and in non-induced K2r/r/tet-O-Cre/CD25f/f mice (regular diet-fed mice).

Conclusions : All three chains of the IL-2R are expressed in the corneal epithelium at the protein level. Our results indicate for the first time that IL-2 regulates corneal epithelial cell proliferation in vitro and that disrupting IL-2 signaling in the cornea leads to dry eye disease in vivo. This effect was only seen in female mice. Future studies are needed to delineate the pathways used by IL-2 signaling to influence cornea homeostasis.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.


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.