ArticlePLoS genetics2015
APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
56 citing papers in PubMed, 4 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- SNTB1 gene polymorphisms and risk of high myopia: meta-analysis and single-center validation.Molecular vision · 2025Pooled it
- A Review of Current Concepts of the Etiology and Treatment of Myopia.Eye & contact lens · 2018Pooled it
- A genome-wide association study of corneal astigmatism: The CREAM Consortium.Molecular vision · 2018Pooled it
- Novel evidence for complement system activation in chick myopia and hyperopia models: a meta-analysis of transcriptome datasets.Scientific reports · 2017Pooled it
- Prevalence and Possible Factors of Myopia in Norwegian Adolescents.Scientific reports · 2018Trial
- Unraveling the Heritability of Ocular Rigidity and Myopia-Related Traits: A Siblings-Based Study.Investigative ophthalmology & visual science · 2026Article
- Increased sensitivity to myopia and altered retinal ON/OFF balance in a mouse model lackingbioRxiv : the preprint server for biology · 2025Article
- Correlation of contrast sensitivity at low spatial frequencies with myopic shift in Chinese children.BMC ophthalmology · 2025Article
- Rapid myopization of the fellow eye in anisometropic amblyopia treated with 1% atropine: a case report.BMC ophthalmology · 2025Article
- Temporal Regulation of Myopia and Inflammation-Associated Pathways in the Interphotoreceptor Retinoid-Binding Protein Knockout Mouse Model.Current eye research · 2025Article
- Myopia development: multifactorial interplay, molecular mechanisms and possible strategies.Frontiers in medicine · 2025Review
- Frequency of myopia and associated risk factors in the adolescent population (10-16 years) of Karachi, Pakistan: a cross-sectional study.BMJ public health · 2025Article
- Article
- A large-scale in vivo screen to investigate the roles of human genes in Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Insights into Myopia from Mouse Models.Annual review of vision science · 2024Review
- Review
- Repeatability and agreement of AOCT-1000 M, RTVue XR and IOL master 500 in measuring corneal thickness mapping and axial length applying principle of optical coherence tomography.BMC medical imaging · 2023Article
- The Role of Retinal Dysfunction in Myopia Development.Cellular and molecular neurobiology · 2023Review
- A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration.EBioMedicine · 2023Article
- Outdoor time influences VIPR2 polymorphism rs2071623 to regulate axial length in Han Chinese children.Molecular vision · 2023Article
Corrections and comments
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Authors and funding
11 authors at 8 institutions in 3 countries.
Funding
Abstract
Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained ("missing heritability"). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5'-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10-4) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10-3). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10-3). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 ± 2.2 D, p < 1.0 × 10-4) compared to both heterozygous (-0.8 ± 2.0 D, p < 1.0 × 10-4) and wild-type (+0.3 ± 2.2 D, p < 1.0 × 10-4) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p < 1.0 × 10-4). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10-4) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the "missing" myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development.
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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.