Abstract
Purpose :
IL-2 is a pleiotropic cytokine that signals through IL-2 receptor α (CD25), β, and γ chains. We reported that CD25 is expressed in the corneal epithelium. CD25 knock-out (KO) mice are a model of Sjögren Syndrome and have decreased corneal axon density and sensitivity. We investigated how CD25 deficiency affects corneal epithelial wound healing.
Methods :
Tears were collected from female and male CD25KO mice and wild-type (WT) littermates and subjected to tear cytokine analysis (VEGF, CXCL1, TNF-α) using Luminex (n=8-11/group). CD25KO and WT mice of both sexes (n=9-12/group) were subjected to unilateral epithelial corneal debridement with a blunt blade. Wound size was visualized and photographed at different time points (1, 20-, 24-, 28-, and 48h and day 14-post-injury) under a microscope using a digital camera after fluorescein instillation. Fluorescein staining gray levels of the right and left corneas were visualized and photographed on day 14 after euthanasia to investigate residual disease.
Results :
Tear VEGF concentration levels were higher in WT than CD25KO mice, irrespectively of sex [485±220 (female) and 204±52 (male) vs. 63±50 (female) and 60±73 pg/mL (male), WT vs. CD25KO mice, respectively, P<0.05]. CXCL1 levels were lower in female WT than male WT mice (140±70 vs.1208±690 pg/mL, respectively, P<0.0001) and decreased in male CD25KO mice (341±280 pg/mL, P<0.0001). TNF-α levels were higher in female CD25KO mice than WT mice (16±7 vs. 7±8 pg/mL, P=0.2). Only female CD25KO mice had delayed cornea reepithelization compared to the WT mice (P<0.0001). The wound size in female CD25KO corneas was 39±41.4% of the original wound size at 48h post-injury. A significant increase in corneal fluorescein staining intensity was observed in the wounded eye of female CD25KO mice compared to WT (520±360 vs.190±51 gray levels, respectively, P<0.0001), while no difference was observed in male mice.
Conclusions :
Female CD25KO mice have decreased VEGF but increased TNF-α levels in tears. Our results indicate that CD25 deficiency results in a sex-specific (female) influence on epithelial wound healing after corneal debridement. Further studies are necessary to dissect the contribution of CD25/IL-2 signaling in the corneal epithelium versus systemic autoimmunity in the CD25KO mice.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.