School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Invest Ophthalmol Vis Sci. 2023 Feb 1;64(2):2. 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.
确定维生素 D3 类似物卡泊三醇在近视发展中的作用，并改变小鼠巩膜 I 型胶原 α1 链（Col1α1）的表达。我们还旨在确定介导上述变化的信号通路是否与转化生长因子β2（TGF-β2）介导的培养人巩膜成纤维细胞（HSF）中 COL1A1 增加的信号通路不同。
C57BL/6J 小鼠经腹腔注射卡泊三醇并进行剥夺（FD）或正常屈光发育 4 周。巩膜维生素 D 受体（Vdr）的表达通过玻璃体内包膜下注射腺相关病毒包装的短发夹 RNA（AAV8-shRNA）来敲低。屈光和生物测量评估近视发展。敲低和诱导策略的结合确定了维生素 D3 和 TGF-β2 信号通路在调节 HSF 中 COL1A1 表达中的相对贡献。
卡泊三醇注射抑制 FD 诱导的近视（FDM），但对正常屈光发育无显著影响。AAV8-shRNA 注射使 Vdr mRNA 表达降低 42%，并使正常眼中的屈光度向近视方向移动（-3.15±0.99D，平均值±SEM）。在 HSF 中，VDR 敲低降低了卡泊三醇诱导的 COL1A1 表达升高，但不改变 TGF-β2 诱导的 COL1A1 表达升高。此外，TGF-β2 增强了卡泊三醇诱导的 COL1A1 表达升高。TGF-β 受体（TGFBRI/II）敲低减弱了 TGF-β2 诱导的 COL1A1 表达升高，而卡泊三醇诱导的 VDR 和 COL1A1 表达水平升高不受影响。
巩膜维生素 D3 通过激活 VDR 依赖性信号通路和增加巩膜 COL1A1 表达水平，抑制小鼠近视发展。
