Molecular mechanism of hypoxia and alpha-ketoglutaric acid on collagen expression in scleral fibroblasts  

作　　者：Yun Sun Zhuo-Zheng Li Jing Yang Ya-Ru Sha Xin-Yu Hou Hong Fu Jia-Yin Li Shu-Chang Bai Yong-Fang Xie Guo-Hui Wang 

机构地区：[1]School of Life Science and Technology,Shandong Second Medical University,Weifang 261053,Shandong Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2024年第10期1780-1790,共11页国际眼科杂志（英文版）

基　　金：Supported by the Natural Science Foundation of Shandong Province,China(No.ZR2023MA069);the Medical and Health Technology Development Project of Shandong Province,China(No.202202050602);College Students’Innovation and Entrepreneurship Training Program(No.S202410438017);the Graduate Student Research Grant from Shandong Second Medical University.

摘　　要：AIM:To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid(α-KG)on scleral collagen expression.METHODS:Meta-analysis and clinical statistics were used to prove the changes in choroidal thickness(ChT)during myopia.The establishment of a hypoxic myopia model(HYP)for rabbit scleral fibroblasts through hypoxic culture and the effects of hypoxia andα-KG on collagen expression were demonstrated by Sirius red staining.Transcriptome analysis was used to verify the genes and pathways that hypoxia andα-KG affect collagen expression.Finally,real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)was used for reverse verification.RESULTS:Meta-analysis results aligned with clinical statistics,revealing a thinning of ChT,leading to scleral hypoxia.Sirius red staining indicated lower collagen expression in the HYP group and higher collagen expression in the HYP+α-KG group,showed that hypoxia reduced collagen expression in scleral fibroblasts,whileα-KG can elevated collagen expression under HYP conditions.Transcriptome analysis unveiled the related genes and signaling pathways of hypoxia andα-KG affect scleral collagen expression and the results were verified by RT-qPCR.CONCLUSION:The potential molecular mechanisms through which hypoxia andα-KG influencing myopia is unraveled and three novel genes TLCD4,TBC1D4,and EPHX3 are identified.These findings provide a new perspective on the prevention and treatment of myopia via regulating collagen expression.

关 键 词：SCLERA scleral collagen expression HYPOXIA alpha-ketoglutaric acid MYOPIA 

分 类 号：R772.3[医药卫生—眼科]