Calcipotriol Attenuates Form Deprivation Myopia Through a Signaling Pathway Parallel to TGF-beta 2-Induced Increases in Collagen Expression

PURPOSE. To determine the role of calcipotriol, a vitamin D3 analogue, in myopia devel-opment and altering the expression of scleral et1 chain of type I collagen (Col1et1) 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 f32 (TGF-f32)-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 contri-butions of the vitamin D3 and the TGF-f32 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-f32-induced increases in COL1A1 expression. Additionally, TGF-f32 augmented calcipotriol-induced rises in COL1A1 expres-sion. TGF-f3 receptor (TGFBRI/II) knockdown blunted TGF-f32-induced increases in COL1A1 expression, whereas calcipotriol-induced increases in VDR and COL1A1 expres-sion 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.