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

Abstract

Purpose 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). Methods 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. Results 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. Conclusions Scleral vitamin D3 inhibits myopia development in mice, potentially by activating a VDR-dependent signaling pathway and increasing scleral COL1A1 expression levels.

Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia

“…Calcitriol can alleviate scleral collagen degradation and change the arrangement of scleral collagen. We speculate that calcitriol may mediate this effect through VDR 26 www.nature.com/scientificreports/ progression but also contributes to the thickening of the choroid and sclera, along with an increase in scleral collagen diameter, providing substantial evidence for the development and application of myopia-preventative pharmaceuticals.…”

Association between serum 25-hydroxyvitamin D level and myopia in children and adolescents: a cross-sectional study

“…In addition, a Dutch study of 6-year-old children showed an association between myopia and high BMI ( 25 ). Obesity often leads to a variety of complications, and one factor associated with myopia is insulin resistance ( 25 , 26 ). Insulin resistance is one of the most common biochemical phenomena associated with obesity, and the suppression of insulin secretion in hyperglycemic states leads to lens thickening, anterior pole shift, and worsening myopia ( 27 ).…”

The Role of Vitamin D3 in Ocular Diseases

“…One of the most recent studies, which aimed to explore the function of vitamin D 3 in myopia development, was carried out on mice. Calcipotriol (a vitamin D 3 analogue) apparently triggers a signaling pathway dependent on the scleral vitamin D receptor, elevating the levels of α1 chain of type I collagen expression in the sclera [ 13 ]. Regarding younger children (aged 5–15 years), there appears to be no remarkable connection between vitamin D deficiency and myopia [ 14 ].…”