ArticleInvestigative ophthalmology & visual science2022
Hypoxia-Induced Scleral HIF-2α Upregulation Contributes to Rises in MMP-2 Expression and Myopia Development in Mice.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Biological mechanisms of atropine in myopia control (Review).Molecular medicine reports · 2026Pooled it
- Effects of Physical Exercise Combined with Accommodative Training on Visual Acuity and Ocular Biometric Parameters in Children Aged 6-7.Life (Basel, Switzerland) · 2026Article
- Scleral Postn Drives Myopia via Promoting Myofibroblast Transdifferentiation.Investigative ophthalmology & visual science · 2026Article
- Gene-Environment Interaction Loci Associated with Refractive Error: SCAMPI Analysis.Ophthalmology science · 2026Article
- Impaired P4HA1-Driven Hydroxyproline Formation Mediates Scleral Collagen Disruption in Form-Deprivation Myopia.Investigative ophthalmology & visual science · 2026Article
- Intermittent myopic visual exposure triggers myopia progression via H3K27me3.Genome medicine · 2026Article
- Hypoxia-responsive self-assembled nanoparticles for reprogramming tumor-associated macrophages into an anti-tumor M1 phenotype in breast cancer.Materials today. Bio · 2026Article
- Rebuilding the degenerative disc microenvironment: mesenchymal stem cells, exosomes, and bioengineered scaffolds.Frontiers in bioengineering and biotechnology · 2026Review
- Hypoxia-induced OPN5 expression is associated with matrix-preserving responses in human scleral fibroblasts.Frontiers in neuroscience · 2026Article
- Aquaporin-1 upregulation is associated with scleral remodeling during myopia development in mice.American journal of translational research · 2026Article
- The key mechanisms and intervention strategies of cell-type-specific mitochondrial metabolism in ophthalmic diseases.Frontiers in cell and developmental biology · 2026Review
- Decreased scleral Wnt5aNature communications · 2025Article
- Mfn2 Regulates Scleral Remodeling in Myopia by Maintaining Endoplasmic Reticulum Homeostasis in Scleral Fibroblasts.Investigative ophthalmology & visual science · 2025Article
- mTOR/HIF-1α-associated scleral metabolic reprogramming by Mingshi formula in form-deprivation myopia.Scientific reports · 2025Article
- Early Peripapillary Choroidal Thinning during Myopia Development: A Potential Biomarker for Progressive Myopia Identified in Tree Shrews.Investigative ophthalmology & visual science · 2025Article
- Mechanism of electroacupuncture involve in lens-induced myopia guinea pigs by inhibiting wnt/β-catenin signaling pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Low-level red light inhibits human retinal pigment epithelial cell fibrosis via UBE2C in a myopia-simulating hypoxic microenvironment.European journal of medical research · 2025Article
- Regulatory Effects of the Wnt7b/β-Catenin/MMP-2 Signaling Pathway on Scleral Stiffness in Guinea Pigs With Form-Deprivation Myopia.Investigative ophthalmology & visual science · 2025Article
- The role of NF-κB pathway and its regulation of inflammatory cytokines in scleral remodeling of form-deprivation mice model.Immunologic research · 2025Article
- An Evidence-Based Narrative Review of Scleral Hypoxia Theory in Myopia: From Mechanisms to Treatments.International journal of molecular sciences · 2025Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Scleral hypoxia is a key factor that induces hypoxia-inducible factor-1α (HIF-1α) upregulation, and this response contributes to myopia progression. Currently, we aim to determine if the different HIF subtypes, including HIF-1α and HIF-2α, mediate hypoxia-induced myopia development through promoting scleral MMP-2 expression and collagen degradation. Methods: Our study included: (1) time-course of scleral HIF-2α, MMP-2, and COL1α1 expression during form-deprivation myopia (FDM) development was determined in C57BL/6J mice. (2) The effect of silencing either HIF-1Α or HIF-2A on hypoxia-induced alterations in MMP-2 expression was analyzed in cultured human scleral fibroblasts (HSFs) under a hypoxic condition (i.e. 1% oxygen). (3) To knock-down either HIF-1α or HIF-2α expression in the sclera, we performed Sub-Tenon's capsule injection of an adeno-associated virus (AAV)8-packaged Cre overexpression vector (AAV8-Cre) in HIF-1αfl/fl or HIF-2αfl/fl mice. HIF-1α, HIF-2α, MMP-2, and COL1α1 expression were analyzed by Western blot or quantitative real-time PCR (qRT-PCR). In addition, the effects of scleral HIF-2α knock-down on normal refractive development and FDM development were evaluated. Results: The time-dependent increases in scleral HIF-2α mimicked the HIF-1α expression profiles as we previously described. Hypoxia significantly promoted MMP-2 expression in HSFs, and this upregulation was solely alleviated by HIF-2A rather than HIF-1A silencing. Scleral HIF-2α knockdown significantly inhibited form-deprivation (FD)-induced MMP-2 upregulation and declines in COL1α1 accumulation and myopia development. Although scleral HIF-1α knockdown also significantly suppressed FD-induced declines in COL1α1 accumulation, it did not abrogate scleral MMP-2 upregulation. Conclusions: HIF-2α rather than HIF-1α induces myopia development through upregulating MMP-2 and promoting collagen degradation in the sclera.
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