title: The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy.
abstract: Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM) is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR) δ had antifibrosis effects in a rat model of corneal damage. Adult Sprague-Dawley rats underwent bilateral phototherapeutic keratectomy (PTK). The eyes were randomized into four groups: PBS, GW501516 (a selective agonist of PPARδ), GSK3787 (a selective antagonist of PPARδ), or GW501516 combined with GSK3787. The agents were subconjunctivally administered twice a week until sacrifice. The cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and postmortem histology. A myofibroblast marker (α-smooth muscle actin) and ECM production (fibronectin, collagen type III and collagen type I) were examined by immunohistochemistry and RT-PCR. At the early stages of wound healing, GW501516 inhibited reepithelialization and promoted angiogenesis. During the remodeling phase of wound healing, GW501516 attenuated the activation and proliferation of keratocytes, which could be reversed by GSK3787. GW501516 decreased transdifferentiation from keratocytes into myofibroblasts, ECM synthesis, and corneal haze. These results demonstrate that GW501516 controls corneal fibrosis and suggest that PPARδ may potentially serve as a therapeutic target for treating corneal scars.
authors.affiliation: Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin 300070, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin 300070, China ; Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Vision Science, Nankai University of Eye Hospital, No. 4 Gansu Road, Heping District, Tianjin 300020, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Tiangeng
authors.initials: T
authors.lastname: He
authors.affiliation: Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin 300070, China ; Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Vision Science, Nankai University of Eye Hospital, No. 4 Gansu Road, Heping District, Tianjin 300020, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin 300070, China ; Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Vision Science, Nankai University of Eye Hospital, No. 4 Gansu Road, Heping District, Tianjin 300020, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hao
authors.affiliation: Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin 300070, China ; Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Vision Science, Nankai University of Eye Hospital, No. 4 Gansu Road, Heping District, Tianjin 300020, China.
authors.forename: Xin
authors.identifier: 0000-0002-9839-6597
authors.initials: X
authors.lastname: Tang