Topical Pigment Epithelium-Derived Factor Suppresses Corneal Epitheliopathy and Inflammation in Dry Eye disease

Abstract

Purpose : Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein widely expressed in different tissues, including the cornea. PEDF has been identified as an effective inhibitor of angiogenic and inflammatory responses. In this study, we aimed to investigate the effect of topical PEDF on disease severity and corneal inflammation in a mouse model of dry eye disease (DED).

Methods : DED was induced in female C57BL/6 mice by placing them in the controlled environment chamber for 14 days. Mice were assigned to one of three groups (n=5 each), to which either 200ng/ml of recombinant PEDF (high dose), 20ng/ml PEDF (low dose) or PBS (control) was administered topically twice per day for 14 days. Corneal fluorescein staining (CFS) was performed to evaluate disease severity. Corneas and draining lymph nodes (dLNs) of different treatment groups were harvested at Day 14. Frequencies of CD45⁺ cells in the cornea, T helper 17 (Th17) and T regulatory (Treg) cells in dLNs, and level of Foxp3 expression by Tregs in dLNs were investigated using flow cytometry.

Results : Both high and low doses of PEDF significantly decreased CFS scores of DED mice at day 7 compared with PBS-treated controls (high-dose vs. control P<0.001; low-dose vs. control P=0.002). At day 7, CFS score of mice treated with high-dose PEDF was significantly lower than those treated with low-dose PEDF (P=0.041). At day 14, high-dose PEDF was associated with a significant decrease in the frequencies of CD45⁺ cells in the cornea compared to PBS-treated controls (P=0.016). However, there was no significant difference in frequencies of Th17 and Treg cells and expression of Foxp3 by Tregs derived from dLNs among three groups.

Conclusions : Our data demonstrate that topical PEDF suppresses corneal inflammation and decreases the severity of DED.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.