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

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.