# Suppression of Cornea Stromal Fibrosis by Vitamin D

## TL;DR

This study shows that two forms of vitamin D can reduce corneal fibrosis in human and mouse cells, offering potential new treatments for vision loss.

## Contribution

The study reveals that 24,25-dihydroxyvitamin D3 has antifibrotic effects even without the vitamin D receptor.

## Key findings

- Both 1,25 and 24,25 vitamin D reduced α-smooth muscle actin levels in corneal cells and organ-cultured corneas.
- 24,25 vitamin D exerted antifibrotic effects in VDR KO cells, suggesting a receptor-independent mechanism.
- VDR KO corneas showed increased fibrosis and reduced immune cell infiltration after injury.

## Abstract

Corneal fibrosis, a significant source of visual impairment, can result from keratocyte-to-myofibroblast transdifferentiation during wound healing. This study investigated the antifibrotic role of 1,25-dihydroxyvitamin D3 (1,25 Vit D) and the lesser-known vitamin D, 24,25-dihydroxyvitamin D3 (24,25 Vit D), in human and mouse corneal stromal cells (HSCs and MSCs) and in a Vit D receptor knockout (VDR KO) mouse model. Cells were treated with TGF-β1 ± Vit D metabolites and the expression of fibrotic and antifibrotic genes and proteins was evaluated. Both metabolites significantly reduced α-smooth muscle actin levels in HSCs, MSCs and organ-cultured mouse corneas (p < 0.05). They also upregulated the mRNA expression of BMP2, BMP6, BMPR2, and TGF-β3, as well as the protein expression of BMP6 and TGF-β3. VDR KO corneas subjected to alkali injury exhibited increased fibrotic responses and reduced CD45+ immune cell infiltration compared to wild-type controls. Notably, 24,25 Vit D exerted antifibrotic effects even in VDR KO cells, and the alternative 24,25 Vit D receptor FAM57B was expressed in all corneal cell layers. These results reveal consistent antifibrotic effects of both 1,25 and 24,25 Vit D across species, support the existence of VDR-independent mechanisms in the cornea, and offer new insights into potential therapeutic strategies for preventing corneal fibrosis.