Evidence map›Paper›PMID 32652319›Full record

ArticleEBioMedicine2020

Scleral HIF-1α is a prominent regulatory candidate for genetic and environmental interactions in human myopia pathogenesis.

Fei Zhao, Dake Zhang, Qingyi Zhou, Fuxin Zhao, Mingguang He, Zhenglin Yang, Yongchao Su, Ying Zhai, Jiaofeng Yan, Guoyun Zhang and 20 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 3 pooled it
9.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 3 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
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  4. Trial
  5. Trial
  6. Review
  7. Article
  8. Role of Autophagy in Scleral Remodeling During Form-Deprivation Myopia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  9. Scleral Postn Drives Myopia via Promoting Myofibroblast Transdifferentiation.Investigative ophthalmology & visual science · 2026
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  11. Article
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  13. Article
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  16. The mClinical epigenetics · 2026
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  20. Review

44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors at 9 institutions in 2 countries.

Fei ZhaoSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Dake ZhangBeijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China; Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, The Chinese Academy of Sciences, Beijing, China.
Qingyi ZhouSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Fuxin ZhaoSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Mingguang HeState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia.
Zhenglin YangThe Key Laboratory for Human Disease Gene Study of Sichuan Province, Department of Clinical Laboratory, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Yongchao SuSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Ying ZhaiSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Jiaofeng YanSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Guoyun ZhangSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Anquan XueSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Jing TangSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Xiaotong HanState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Yi ShiThe Key Laboratory for Human Disease Gene Study of Sichuan Province, Department of Clinical Laboratory, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Yun ZhuSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Tianzi LiuKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, The Chinese Academy of Sciences, Beijing, China.
Wenjuan ZhuangPeople's Hospital of Ningxia Hui Autonomous Region, Ningxia Eye Hospital (First Affiliated Hospital of Northwest University For Nationalities), Yinchuan, Ningxia, China.
Lulin HuangThe Key Laboratory for Human Disease Gene Study of Sichuan Province, Department of Clinical Laboratory, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Yaqiang HongKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, The Chinese Academy of Sciences, Beijing, China.
Deng WuKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, The Chinese Academy of Sciences, Beijing, China.
Yingxiang LiWeGene, Inc, Shenzhen, Guangdong, China.
Qinkang LuOphthalmology Center of Yinzhou People's Hospital, Ningbo, Zhejiang, China.
Wei ChenBeijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China; Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, The Chinese Academy of Sciences, Beijing, China.
Shiming JiaoSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Qiongsi WangSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Nethrajeith SrinivasaluSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Yingying WenSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Changqing ZengKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, The Chinese Academy of Sciences, Beijing, China.
Jia QuSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China.
Xiangtian ZhouSchool of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China. Electronic address: zxt@mail.eye.ac.cn.
Affiliated Eye Hospital of Wenzhou Medical College · CNWenzhou Medical University · CNBeijing Institute of Genomics · CNUniversity of Electronic Science and Technology of China · CNBeihang University · CNCentre for Eye Research Australia · AUChinese Academy of Sciences · CNNorthwest University · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyopia is a good model for understanding the interaction between genetics and environmental stimuli. Here we dissect the biological processes affecting myopia progression.

methodsHuman Genetic Analyses: (1) gene set analysis (GSA) of new genome wide association study (GWAS) data for 593 individuals with high myopia (refraction ≤ -6 diopters [D]); (2) over-representation analysis (ORA) of 196 genes with de novo mutations, identified by whole genome sequencing of 45 high-myopia trio families, and (3) ORA of 284 previously reported myopia risk genes. Contributions of the enriched signaling pathways in mediating the genetic and environmental interactions during myopia development were investigated in vivo and in vitro.

resultsAll three genetic analyses showed significant enrichment of four KEGG signaling pathways, including amphetamine addiction, extracellular matrix (ECM) receptor interaction, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton pathways. In individuals with extremely high myopia (refraction ≤ -10 D), the GSA of GWAS data revealed significant enrichment of the HIF-1α signaling pathway. Using human scleral fibroblasts, silencing the key nodal genes within protein-protein interaction networks for the enriched pathways antagonized the hypoxia-induced increase in myofibroblast transdifferentiation. In mice, scleral HIF-1α downregulation led to hyperopia, whereas upregulation resulted in myopia. In human subjects, near work, a risk factor for myopia, significantly decreased choroidal blood perfusion, which might cause scleral hypoxia.

interpretationOur study implicated the HIF-1α signaling pathway in promoting human myopia through mediating interactions between genetic and environmental factors.

fundingNational Natural Science Foundation of China grants; Natural Science Foundation of Zhejiang Province.

Indexed as

Gene-Environment InteractionGenetic Predisposition to DiseaseAnimalsDisease Models, AnimalFemaleGenome-Wide Association StudyHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMiceMyopiaScleraSignal TransductionHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitGenetic and environmental interactionsHIF-1αMyopiaMyopia risk genesNear workSclera

Identifiers

PMID32652319
PMCPMC7348000
OpenAlexW3041221900

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.