Hyperosmolar Potassium Inhibits Corneal Myofibroblast Transformation and Prevent Corneal Scar

Abstract

PurposeCorneal myofibroblasts play a crucial role in the process of corneal scarring. Potassium has been documented to reduce skin scar tissue formation. Herein, we investigated the ability of potassium to prevent corneal fibrosis in cell culture and in vivo.MethodsCorneal fibroblasts (CFs) were isolated from the corneal limbus and treated with TGF-β1 to transform into corneal myofibroblasts. Corneal myofibroblast markers were detected by quantitative real-time PCR, Western blot, and immunofluorescence. The contractive functions of corneal myofibroblast were evaluated by the scratch assay and the collagen gel contraction assay. RNA sequencing in corneal fibroblasts was performed to explore the mechanisms underlying hyperosmolar potassium treatment. GO and KEGG analysis were performed to explore the underlying mechanism by hyperosmolar potassium treatment. The ATP detection assay assessed the level of cell metabolism. KCl eye drops four times per day were administered to mice models of corneal injury to evaluate the ability to prevent corneal scar formation. Corneal opacity area was evaluated by Image J software.ResultsTreatment with hyperosmolar potassium could suppress corneal myofibroblast transformation and collagen I synthesis induced by TGF-β1 in cell culture. Hyperosmolar potassium could inhibit wound healing and gel contraction in CFs. RNA sequencing results suggested that genes involved in the metabolic pathway were downregulated after KCl treatment. ATP levels were significantly decreased in the KCl group compared with the control group. Hyperosmolar potassium could prevent corneal myofibroblast transformation after corneal injury and corneal scar formation in mice.ConclusionPotassium can suppress corneal myofibroblast transformation and collagen I protein synthesis. Moreover, given that KCl eye drops can prevent corneal scar formation, it has been suggested to have huge prospects as a novel treatment approach during clinical practice.