Exploring Cornea Endothelium Regeneration with Selective WNT Mimetics

Abstract

Purpose : Cornea endothelial dystrophies involve a gradual decline in cornea endothelial cell numbers and function. A dysfunctional endothelial cell layer can result in edema, corneal opacity, pain, and blindness. These symptoms can occur in Fuchs’ dystrophy or following cataract surgery. Cornea endothelial cells in human are considered post mitotic in normal conditions and have limited regenerative capacity. A therapeutic approach to stimulate endothelial cell proliferation would have the potential to treat endothelial dystrophies. Here, we ask whether WNT signaling activation using a recombinant WNT mimetic platform can activate cornea endothelial cells and restore vision.

Methods : Cultured human corneal endothelial cells or total human cornea explants were used to model proliferation in vitro. Trans corneal freezing was used as cryoinjury induced edema in mice. Treatment groups for both in vitro and in vivo experiments consisted of antibody based WNT mimetic and controls.

Results : Frizzled and LRP5/6 receptors, essential for WNT signal transduction, are expressed in endothelial cells in both mouse and human. Using two different ex vivo human culture platforms we demonstrate a pro-proliferative effect of WNT mimetic treatment. We demonstrate that local WNT mimetic treatment reduces corneal edema in a trans corneal freezing model of endothelial cell loss.

Conclusions : Our findings extend the potential of WNT pathway activation using a mimetics platform to stimulate endothelial cell proliferation. Together, this study provides a novel approach to treat cornea endothelial dystrophies.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.