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

• Published in: Investigative ophthalmology & visual science 2023-02, Vol.64 (2), p.2-2
• Main Authors: Jiao, Shiming, Reinach, Peter Sol, Huang, Chengjie, Yu, Lan, Zhuang, Huiman, Ran, Hongli, Zhao, Fei, Srinivasalu, Nethrajeith, Qu, Jia, Zhou, Xiangtian
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry and Molecular Biology; Calcitriol - metabolism; Calcitriol - pharmacology; Collagen - metabolism; Humans; Mice; Mice, Inbred C57BL; Myopia - genetics; Sclera - metabolism; Signal Transduction; Transforming Growth Factor beta2 - metabolism; Transforming Growth Factor beta2 - pharmacology
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.64.2.2

To determine the role of calcipotriol, a vitamin D3 analogue, in myopia development and altering the expression of scleral α1 chain of type I collagen (Col1α1) in mice. We also aimed to identify if the signaling pathway mediating the above changes is different from the one involved in transforming growth factor β2 (TGF-β2)-mediated increases of COL1A1 in cultured human scleral fibroblasts (HSFs). C57BL/6J mice were either intraperitoneally injected with calcipotriol and subjected to form deprivation (FD) or exposed to normal refractive development for 4 weeks. Scleral vitamin D receptor (Vdr) expression was knocked down using a Sub-Tenon's capsule injection of an adeno-associated virus-packaged short hairpin RNA (AAV8-shRNA). Refraction and biometric measurements evaluated myopia development. A combination of knockdown and induction strategies determined the relative contributions of the vitamin D3 and the TGF-β2 signaling pathways in modulating COL1A1 expression in HSFs. Calcipotriol injections suppressed FD-induced myopia (FDM), but it had no significant effect on normal refractive development. AAV8-shRNA injection reduced Vdr mRNA expression by 42% and shifted the refraction toward myopia (-3.15 ± 0.99D, means ± SEM) in normal eyes. In HSFs, VDR knockdown reduced calcipotriol-induced rises in COL1A1 expression, but it did not alter TGF-β2-induced increases in COL1A1 expression. Additionally, TGF-β2 augmented calcipotriol-induced rises in COL1A1 expression. TGF-β receptor (TGFBRI/II) knockdown blunted TGF-β2-induced increases in COL1A1 expression, whereas calcipotriol-induced increases in VDR and COL1A1 expression levels were unaltered. Scleral vitamin D3 inhibits myopia development in mice, potentially by activating a VDR-dependent signaling pathway and increasing scleral COL1A1 expression levels.