Identification of LRRC46 as a novel candidate gene for high myopia

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外文摘要：High myopia(HM)is the primary cause of blindness,with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues.In a previously reported myopic linkage region,MYP5(17q21-22),a potential candidate gene,LRRC46(c.C235T,p.Q79X),was identified in a large Han Chinese pedigree.LRRC46 is expressed in various eye tissues in humans and mice,including the retina,cornea,and sclera.In subsequent cell experiments,the mutation(c.C235T)decreased the expression of LRRC46 protein in human corneal epithelial cells(HCE-T).Further investigation revealed that Lrrc46-/-mice(KO)exhibited a classical myopia phenotype.The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age,the activity of limbal stem cells decreased,and microstructural changes were observed in the fibroblasts of the sclera and cornea.We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type(WT)mice,which indicated a significant downregulation of the collagen synthesis-related pathway(extracellular matrix,ECM)in KO mice.Subsequent in vitro studies further indicated that LRRC46,a member of the important LRR protein family,primarily affected the formation of collagens.This study suggested that LRRC46 is a novel candidate gene for HM,influencing collagen protein Ⅷ(Col8a1)formation in the eye and gradually altering the biomechanical structure of the cornea and sclera,thereby promoting the occurrence and development of HM.

外文关键词：

high myopiaLRRC46biomechanicscollagen protein Ⅷ

作者：

Lingxi Jiang、Chao Dai、Yao Wei、Bo Zhao、Qi Li、Zhengzheng Wu、Liang Zou、Zimeng Ye、Zhenglin Yang、Lulin Huang、Yi Shi

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作者单位：

Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics,Department of Laboratory Medicine,Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China,Chengdu 610072,China

Department of Ophthalmology,Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China,Chengdu 610072,China

School of Food and Bioengineering,Chengdu University,Chengdu 610106,China

School of Medicine,University of Sydney,Sydney 2050,Australia

Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019R

Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026),Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital,Chengdu 610072,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCAMS Innovation Fund for Medical SciencesCAMS Innovation Fund for Medical SciencesSichuan Science and Technology ProgramSichuan Science and Technology ProgramSichuan Science and Technology ProgramSichuan Science and Technology ProgramSichuan Science and Technology ProgramSichuan Science and Technology Program

项目编号：

823300308227112082121003822012342019-12 M-5-0322021LY062021YFS03692022ZYD013124YSZH001223ZYZYTS0271TB20230932023ZY0059

出版年：

2024

DOI：

10.1007/s11427-024-2583-6

中国科学:生命科学(英文版)

中国科学院

中国科学:生命科学(英文版)

CSTPCD

影响因子：0.806

ISSN：1674-7305

年,卷(期)：2024.67(9)