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Title: IL-20 promotes epithelial healing of the injured mouse cornea

item ZHANG, WANYU - University Of Houston
item MAGADI, SRI - University Of Houston
item LI, ZHIJIE - Children'S Nutrition Research Center (CNRC)
item SMITH, C WAYNE - Children'S Nutrition Research Center (CNRC)
item BURNS, ALAN - University Of Houston

Submitted to: Experimental Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2016
Publication Date: 11/3/2016
Citation: Zhang, W., Magadi, S., Li, Z., Smith, C., Burns, A.R. 2016. IL-20 promotes epithelial ealing of the injured mouse cornea. Experimental Eye Research. 154:22-29.

Interpretive Summary: It is well known that diabetics are susceptible to progressive loss of normal clarity in the clear surface of the eye, the cornea. In order to understand how this happens, it is necessary to understand the mechanisms that normally keep the cornea healthy. This research paper reveals a previously unknown normal mechanism that plays an important role for for white blood cells in the cornea. These cells are very important for tissue repair during normal aging or after injury. The current study demonstrates in a mouse model of corneal wounds that injured corneal cells produce interleukin-20 (IL-20), a protein that is necessary for proper function of the activated white blood cells. This finding provides a basis for our future studies analyzing the effects of a diet that promotes diabetes on the production and function of IL-20 in the cornea.

Technical Abstract: After corneal epithelial injury, the ensuing inflammatory response is necessary for efficient wound healing. While beneficial healing effects are attributed to recruited neutrophils and platelets, dysregulated inflammation (too little or too much) is associated with impaired wound healing. The purpose of this study was to use an established C57BL/6J mouse model of corneal injury to evaluate the potential modulatory role of interleukin-20 on the inflammatory and healing responses to epithelial wounding. In the uninjured cornea, immunofluorescence staining for interleukin-20 and its receptor, interleukin-20RA, was observed on basal epithelial cells at the limbus. After a 2mm central epithelial abrasion, interleukin-20 staining was also observed in stromal keratocytes and ELISA studies showed a significant increase (nearly 3-fold) in interleukin-20 expression. Injured corneas healed more slowly when treated with a topical application of a neutralizing anti-interleukin-20 antibody. While corneal epithelial cell division and epithelial nerve recovery measured at 24 h post-injury were reduced compared to controls, neutrophil influx into the cornea was increased. In contrast, topical application of recombinant interleukin-20 decreased corneal inflammation as evidenced by reductions in limbal vessel dilatation, platelet extravasation, neutrophil recruitment and CXCL1 expression. In wild type mice, topical recombinant interleukin-20 had a limited effect on corneal wound healing and resulted in only a slight increase in epithelial cell division and epithelial nerve recovery; the rate of wound closure was unaffected. To clarify the effect of interleukin-20 on corneal wound healing, recombinant interleukin-20 was topically applied to neutropenic wild type mice and mutant mice (delta T cell deficient mice and CD11a deficient mice), all of which have well characterized reductions in neutrophil recruitment and delayed wound healing after corneal injury. In each case, recombinant interleukin-20 restored corneal wound healing to baseline levels while neutrophil recruitment remained low. Thus, it appears that interleukin-20 plays a beneficial and direct role in corneal wound healing while negatively regulating neutrophil and platelet infiltration.