PMID- 36723926 OWN - NLM STAT- MEDLINE DCOM- 20230203 LR - 20230217 IS - 1552-5783 (Electronic) IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 64 IP - 2 DP - 2023 Feb 1 TI - Calcipotriol Attenuates Form Deprivation Myopia Through a Signaling Pathway Parallel to TGF-beta2-Induced Increases in Collagen Expression. PG - 2 LID - 10.1167/iovs.64.2.2 [doi] LID - 2 AB - PURPOSE: To determine the role of calcipotriol, a vitamin D3 analogue, in myopia development and altering the expression of scleral alpha1 chain of type I collagen (Col1alpha1) 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 beta2 (TGF-beta2)-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-beta2 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-beta2-induced increases in COL1A1 expression. Additionally, TGF-beta2 augmented calcipotriol-induced rises in COL1A1 expression. TGF-beta receptor (TGFBRI/II) knockdown blunted TGF-beta2-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. FAU - Jiao, Shiming AU - Jiao S AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Reinach, Peter Sol AU - Reinach PS AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Huang, Chengjie AU - Huang C AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Yu, Lan AU - Yu L AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Zhuang, Huiman AU - Zhuang H AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Ran, Hongli AU - Ran H AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Zhao, Fei AU - Zhao F AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Research Unit of Myopia Basic Research and Clinical Prevention and Control, Chinese Academy of Medical Sciences, Wenzhou, Zhejiang, China. AD - Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou, Zhejiang, China. AD - National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, China. FAU - Srinivasalu, Nethrajeith AU - Srinivasalu N AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Qu, Jia AU - Qu J AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou, Zhejiang, China. AD - National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, China. FAU - Zhou, Xiangtian AU - Zhou X AD - School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Research Unit of Myopia Basic Research and Clinical Prevention and Control, Chinese Academy of Medical Sciences, Wenzhou, Zhejiang, China. AD - Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou, Zhejiang, China. AD - National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Transforming Growth Factor beta2) RN - 143NQ3779B (calcipotriene) RN - 9007-34-5 (Collagen) RN - FXC9231JVH (Calcitriol) SB - IM MH - Humans MH - Animals MH - Mice MH - *Transforming Growth Factor beta2/pharmacology/metabolism MH - Mice, Inbred C57BL MH - Collagen/metabolism MH - Calcitriol/pharmacology/metabolism MH - Signal Transduction MH - *Myopia/genetics MH - Sclera/metabolism PMC - PMC9904334 COIS- Disclosure: S. Jiao, None; P.S. Reinach, None; C. Huang, None; L. Yu, None; H. Zhuang, None; H. Ran, None; F. Zhao, None; N. Srinivasalu, None; J. Qu, None; X. Zhou, None EDAT- 2023/02/02 06:00 MHDA- 2023/02/04 06:00 PMCR- 2023/02/01 CRDT- 2023/02/01 11:33 PHST- 2023/02/01 11:33 [entrez] PHST- 2023/02/02 06:00 [pubmed] PHST- 2023/02/04 06:00 [medline] PHST- 2023/02/01 00:00 [pmc-release] AID - 2785322 [pii] AID - IOVS-22-35560 [pii] AID - 10.1167/iovs.64.2.2 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2023 Feb 1;64(2):2. doi: 10.1167/iovs.64.2.2.