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利用重组人骨形态发生蛋白2的潜力:调节近视豚鼠的巩膜变化

Harnessing the potential of recombinant human BMP2: regulating scleral changes in myopic guinea pigs.

作者信息

Liu Yijie, Hao Qi, Pan Xuemei, Wang Pubo, Guo Dadong, Tian Qingmei, Zhang Xiuyan, Lu Xiuzhen, Wu Qiuxin, Bi Hongsheng

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

Shandong Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Shandong Academy of Eye Disease Prevention and Therapy, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

出版信息

Front Med (Lausanne). 2025 May 1;12:1526656. doi: 10.3389/fmed.2025.1526656. eCollection 2025.

DOI:10.3389/fmed.2025.1526656
PMID:40375931
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12078322/
Abstract

Studies have shown that the development of myopia is associated with scleral remodeling, but the exact mechanism is not yet clear. This study investigates the effects of vitreous injection of recombinant human bone morphogenetic protein 2 (rhBMP2) on scleral remodeling in myopic guinea pigs and the possible signaling pathways. Guinea pigs were randomly divided into normal control (NC) group, lens-induced myopia (LIM) group, rhBMP2 low-dose group (LD), rhBMP2 medium-dose group (MD), and rhBMP2 high-dose group (HD). After rhBMP2 intervention, myopic refraction was reduced and axial growth was delayed compared with the LIM group; Hematoxylin-eosin (H&E) staining showed that the arrangement of scleral collagen fibers was loose, the disorder was improved, and the cavities were reduced, especially in MD group; and immunofluorescence staining showed elevated -SMA protein expression. Q-PCR and western blot results showed that after rhBMP2 intervention, at the mRNA and protein levels, the expression of BMPRIA, smad1, smad5, smad9, smad4, TIMP2, and Col1A1 was up-regulated, and MMP2 expression was down-regulated when compared with the LIM group. From this study, we conclude that after injecting rhBMP2 into the vitreous cavity of experimental myopic guinea pigs, it can bind to BMP2-related receptors, activate smad signaling pathway, affect the expression of MMP2/TIMP2, promote the expression of Col1A1 gene, regulate scleral remodeling, promote collagen I synthesis, and delay the development of myopia.

摘要

研究表明,近视的发展与巩膜重塑有关,但确切机制尚不清楚。本研究探讨玻璃体注射重组人骨形态发生蛋白2(rhBMP2)对近视豚鼠巩膜重塑的影响及可能的信号通路。将豚鼠随机分为正常对照组(NC)、晶状体诱导性近视组(LIM)、rhBMP2低剂量组(LD)、rhBMP2中剂量组(MD)和rhBMP2高剂量组(HD)。rhBMP2干预后,与LIM组相比,近视屈光度降低,眼轴生长延迟;苏木精-伊红(H&E)染色显示巩膜胶原纤维排列疏松,紊乱改善,腔隙减少,尤其是MD组;免疫荧光染色显示α-SMA蛋白表达升高。Q-PCR和western blot结果显示,rhBMP2干预后,与LIM组相比,在mRNA和蛋白水平上,BMPRIA、smad1、smad5、smad9、smad4、TIMP2和Col1A1的表达上调,MMP2表达下调。从本研究中,我们得出结论,向实验性近视豚鼠玻璃体腔注射rhBMP2后,它可以与BMP2相关受体结合,激活smad信号通路,影响MMP2/TIMP2的表达,促进Col1A1基因的表达,调节巩膜重塑,促进I型胶原合成,并延缓近视的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/db3666212877/fmed-12-1526656-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/28e79f5c06d8/fmed-12-1526656-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/a949140b4827/fmed-12-1526656-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/ae0c82e1ff65/fmed-12-1526656-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/cfffe9204c6d/fmed-12-1526656-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/db3666212877/fmed-12-1526656-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/28e79f5c06d8/fmed-12-1526656-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/a949140b4827/fmed-12-1526656-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/ae0c82e1ff65/fmed-12-1526656-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/cfffe9204c6d/fmed-12-1526656-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7062/12078322/db3666212877/fmed-12-1526656-g005.jpg

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本文引用的文献

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Mol Med. 2024 Feb 14;30(1):25. doi: 10.1186/s10020-024-00795-x.
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Mechanism of annexin A1/N-formylpeptide receptor regulation of macrophage function to inhibit hepatic stellate cell activation through Wnt/β-catenin pathway. annexin A1/N-甲酰肽受体调控巨噬细胞功能抑制肝星状细胞活化的机制通过 Wnt/β- 连环蛋白通路。
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Scleral Remolding-Related Gene Expression After Scleral Collagen Cross-Linking Using Ultraviolet A and Riboflavin in Myopic Guinea Pig Model.
在近视豚鼠模型中,使用紫外线A和核黄素进行巩膜胶原交联后与巩膜重塑相关的基因表达
Curr Eye Res. 2023 Apr;48(4):392-401. doi: 10.1080/02713683.2022.2156549. Epub 2022 Dec 15.
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Altered Structure and Function of Murine Sclera in Form-Deprivation Myopia.形觉剥夺性近视小鼠巩膜结构和功能的改变。
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Electroacupuncture Improves Choroidal Blood Flow to Inhibit the Development of Lens-Induced Myopia in Guinea Pigs.电针改善豚鼠脉络膜血流以抑制晶状体诱导性近视的发展。
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[Epidemiology of myopia].[近视流行病学]
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Form-deprivation myopia induces decreased expression of bone morphogenetic protein-2, 5 in guinea pig sclera.形觉剥夺性近视导致豚鼠巩膜中骨形态发生蛋白-2、5的表达降低。
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