Evidence map›Paper›PMID 42010709›Full record

ArticleGenome medicine2026

Intermittent myopic visual exposure triggers myopia progression via H3K27me3.

Yi Lei, Xiaolei Lin, Xuemei Ling, Yuhan Tan, Jian Yuan, Yating Li, Mengqi Di, Yulu Pan, Lurong Zhong, Zhaoning Feng and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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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

1 citing paper in PubMed.

  1. Article
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

19 authors.

Yi Lei *State Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Xiaolei Lin *State Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Xuemei Ling *State Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Yuhan Tan *State Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Jian Yuan *State Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Yating LiState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Mengqi DiState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Yulu PanState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Lurong ZhongState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Zhaoning FengState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Fangfang JiaoState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Changxi HuState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Hanyu DengState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Miaozhen PanState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Jianzhong SuState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Jia QuState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. qujia@eye.ac.cn.
Wei ChenBeijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Engineering Medicine, Beihang University, Beijing, 100191, China. chenw123@buaa.edu.cn.
Fei ZhaoState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. zhaofei@eye.ac.cn.
Xiangtian ZhouState Key Laboratory of Eye Health, Oujiang Laboratory, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. zhouxt@shsmu.edu.cn.

Funding

Beijing Natural Science Foundation grant 5232014National Natural Science Foundation of China 32571524National Natural Science Foundation of China 82000934National Natural Science Foundation of China 82025009 , 82388101 , U23A20438National Natural Science Foundation of China 82201232National Natural Science Foundation of China 82422019 , 82171097National Natural Science Foundation of China U20A20364Natural Science Foundation of Zhejiang Province Y23H120009Shanghai Eye Disease Research Center 2022ZZ01003
6 · The paper itself

Abstract

backgroundMyopia is a global epidemic and a leading cause of visual impairment. It is driven by intermittent environmental exposures, such as near-work, which induce scleral hypoxia. However, the molecular mechanism that translates these transient stimuli into sustained myopia progression remains elusive. We hypothesized that intermittent myopiagenic exposures establish stable pathological changes in the sclera that contribute to myopia development.

methodsWe integrated human genetic data from the Myopia Associated Genetics and Intervention Consortium (MAGIC) cohort and the UK Biobank to identify epigenetic factors associated with myopia. Findings were validated in mouse and guinea pig form-deprivation myopia (FDM) models. Intermittent form-deprivation (iFD) protocols were established to investigate how specific epigenetic modifications sustain persistent chromatin remodeling and drive myopia progression. Mechanistic investigations employed Adeno-associated virus serotype 8 (AAV8)-mediated gene knockdown or overexpression, CUT&Tag, RNA-seq, primary human scleral fibroblasts (HSFs) cultures, and protein interaction assays (co-immunoprecipitation and proximity ligation assays).

resultsHuman myopia genetics reveals significant enrichment of H3K27me3 regulators and targets within myopia-associated loci. FDM models in mice and guinea pigs exhibit an increase in H3K27me3 level and declines in the protein levels of its specific demethylases, KDM6A and KDM6B, in the sclera. Using complementary "intermittent recovery-based inhibition of myopiagenesis" and "intermittent myopiagenic stimulus-induced myopia" models, we demonstrated that increasing the scleral content of H3K27me3, but not of hypoxia-inducible factor-1α (HIF-1α), is necessary for myopiagenesis. Mechanistically, hypoxia decreases deubiquitinase USP16 content while increasing E3 ligase NEDD4 content, leading to the proteasomal degradation of KDM6A and subsequent H3K27me3 accumulation. Gain or loss of scleral H3K27me3 function, respectively induced or suppressed collagen loss and myopia development. Furthermore, H3K27me3 repressed Sp1 transcription, decreasing scleral collagen content and enabling myopia development.

conclusionsOur findings suggested that scleral H3K27me3 is an epigenetic mediator that connects intermittent myopiagenic exposures to persistent chromatin remodeling and myopia progression. The data support a model involving the " KDM6A-H3K27me3-Sp1" axis, providing a molecular framework for understanding the cumulative biological effects of myopiagenic risk factors.

Indexed as

HistonesMyopiaAnimalsDisease Models, AnimalDisease ProgressionEpigenesis, GeneticFemaleFibroblastsGuinea PigsHumansMaleMiceScleraHistonesH3K27me3Hypoxiaintermittent myopiagenic exposureKDM6AMyopiaSclera

Identifiers

PMID42010709
PMCPMC13224520

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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.