# TGF-β Promotes Endothelial-to-Mesenchymal Transition and Alters Corneal Endothelial Cell Migration in Fuchs Endothelial Corneal Dystrophy

## TL;DR

This study shows that TGF-β signaling promotes EndoMT and increases cell migration in corneal endothelial cells affected by Fuchs dystrophy.

## Contribution

The study reveals how TGF-β1 and TGF-β2 drive EndoMT and alter migration in corneal endothelial cells in Fuchs dystrophy.

## Key findings

- TGF-β2 levels are significantly elevated in the aqueous humor of FECD patients.
- TGF-β1 and TGF-β2 increase EMT markers and promote an EMT-like phenotype in FECD and control cells.
- TGF-β signaling increases migration speed and alters migration behavior in FECD corneal endothelial cells.

## Abstract

Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease characterized by corneal endothelial cell (CEC) loss and guttae formation. Elevated levels of Transforming Growth Factor-Beta 1 and 2 (TGF-β1/-β2) have been reported in the aqueous humor (AH) of FECD patients and have been implicated with abnormal extracellular matrix (ECM) production, endothelial-to-mesenchymal transition (EndoMT), the unfolded protein response, and cell death. However, how TGF-β signaling affects cell migration in FECD remains to be elucidated. In this study, we found that TGF-β2 levels were significantly elevated in the AH of FECD patients compared to controls. We performed bulk RNA sequencing on FECD CECs treated with TGF-β1 or TGF-β2 and identified the epithelial-to-mesenchymal (EMT) pathway as one of the top dysregulated pathways. We found that TGF-β1 and TGF-β2 increased EMT markers, filamentous-actin (F-actin) expression and produced more EMT-like phenotype in FECD and control CECs. We also observed that TGF-β1 and TGF-β2 significantly increased FECD CEC migration speed as detected by scratch assay and individual cell tracking and promoted individual cellular migration behavior. This study provides novel insight into FECD pathogenesis and how increased TGF-β signaling promotes EndoMT and alters cellular migration in FECD CECs.