Calcipotriol Attenuates Form Deprivation Myopia Through a Signaling Pathway Parallel to TGF-β2-Induced Increases in

Shiming Jiao1,2, Peter Sol Reinach1,2, Chengjie Huang1,2

  • 1School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract

Insights

Vitamin D3 analogue calcipotriol inhibits myopia development in mice by increasing scleral collagen type I alpha 1 (COL1A1) expression via a vitamin D receptor (VDR)-dependent pathway.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Pharmacology

Background:

  • Myopia, a global health concern, is influenced by scleral structural changes.
  • Vitamin D and its analogues are being investigated for their potential roles in ocular development and disease.
  • Scleral collagen type I alpha 1 (COL1A1) is crucial for maintaining scleral rigidity and plays a role in myopia progression.

Purpose of the Study:

  • To investigate the effect of calcipotriol, a vitamin D3 analogue, on myopia development in mice.
  • To determine calcipotriol's influence on scleral COL1A1 expression.
  • To compare the signaling pathways of vitamin D3 and transforming growth factor β2 (TGF-β2) in modulating COL1A1 expression.

Main Methods:

  • Myopia was induced in C57BL/6J mice using form deprivation (FD) and treated with calcipotriol.
  • Scleral vitamin D receptor (Vdr) expression was knocked down using adeno-associated virus-packaged short hairpin RNA (AAV8-shRNA).
  • Human scleral fibroblasts (HSFs) were used to study the effects of calcipotriol and TGF-β2 on COL1A1 expression, with and without VDR or TGF-β receptor knockdown.

Main Results:

  • Calcipotriol injections suppressed form deprivation-induced myopia (FDM) in mice.
  • Vitamin D receptor (Vdr) knockdown exacerbated myopia development in normal eyes.
  • In HSFs, VDR knockdown reduced calcipotriol-induced COL1A1 expression but did not affect TGF-β2-induced COL1A1 expression, suggesting distinct pathways.

Conclusions:

  • Scleral vitamin D3, via calcipotriol, inhibits myopia development in mice.
  • This inhibition is potentially mediated by activating a VDR-dependent signaling pathway.
  • Increased scleral COL1A1 expression is a key outcome of this vitamin D3-mediated pathway.