Anti-Angiogenic and Anti-Scarring Dual Effect of Galectin-3 Inhibition in Mouse Models of Corneal Wound Healing

Abstract

Corneal scarring is the third leading cause of global blindness. Neovascularization of ocular tissues is a major predisposing factor for scar development. Although corneal transplantation is effective at restoring vision, some patients are at high risk of graft rejection due to the presence of blood vessels in the injured cornea. Current treatment options to control corneal scarring are limited and their outcomes are typically poor. In this study, using mouse models of corneal wound healing, we demonstrate that topical application of a small molecule inhibitor of galectin-3, GB1265: reduces (i) corneal angiogenesis, (ii) corneal fibrosis, (iii) infiltration of immune cells and (iv) expression of proinflammatory cytokine, IL-1β, in injured corneas. Four independent techniques (RNA-seq, NanoString, RT-qPCR, and Western blot analyses) all demonstrated that decrease in corneal opacity in the galectin-3 inhibitor-treated corneas is associated with a decrease in a number of genes and signaling pathways that are known to promote fibrosis. These findings allow us to place a high level of confidence in our conclusion that galectin-3 inhibition by a small molecule inhibitor, GB1265, has dual anti-angiogenic and anti-scarring effect. Targeting galectin-3 by GB1265, is thus, an attractive strategy for development of innovative treatment of myriad of ocular and nonocular diseases characterized by pathological angiogenesis and fibrosis.