ArticleInvestigative ophthalmology & visual science2008
HIF-1: an age-dependent regulator of lens cell proliferation.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Stem cell-derived extracellular vesicles enriched with miR-22-3p for cataract treatment - Molecular mechanisms and therapeutic potential: A review.Biomolecules & biomedicine · 2026Review
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- The 3D Genome Structure of a Blcap-Linked Silencer Loop Regulates Terminal Differentiation During Lens Fiber Cell Denucleation.Investigative ophthalmology & visual science · 2025Article
- Hypoxia-Driven Histone Modifications Govern Gene Regulation for Mature Eye Lens Formation.Investigative ophthalmology & visual science · 2025Article
- Age-Related Differences in the Mouse Corneal Epithelial Transcriptome and Their Impact on Corneal Wound Healing.Investigative ophthalmology & visual science · 2024Article
- Article
- Multiomics Analysis Reveals Novel Genetic Determinants for Lens Differentiation, Structure, and Transparency.Biomolecules · 2023Review
- Dynamic changes in whole genome DNA methylation, chromatin and gene expression during mouse lens differentiation.Epigenetics & chromatin · 2023Article
- Markers of Hypoxia and Metabolism Correlate With Cell Differentiation in Retina and Lens Development.Frontiers in ophthalmology · 2022Article
- A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.BMC genomics · 2021Article
- Hypoxia regulates the degradation of non-nuclear organelles during lens differentiation through activation of HIF1a.Experimental eye research · 2020Article
- Lens differentiation is characterized by stage-specific changes in chromatin accessibility correlating with differentiation state-specific gene expression.Developmental biology · 2019Article
- The role of HIF-1α in the TGF-β2-mediated epithelial-to-mesenchymal transition of human lens epithelial cells.Journal of cellular biochemistry · 2018Article
- Lens-specific deletion of the Msx2 gene increased apoptosis by enhancing the caspase-3/caspase-8 signaling pathway.The Journal of international medical research · 2018Article
- Signaling and Gene Regulatory Networks in Mammalian Lens Development.Trends in genetics : TIG · 2017Review
- Intrinsic and extrinsic regulatory mechanisms are required to form and maintain a lens of the correct size and shape.Experimental eye research · 2017Review
- Birc7: A Late Fiber Gene of the Crystalline Lens.Investigative ophthalmology & visual science · 2015Article
- Dual function of Yap in the regulation of lens progenitor cells and cellular polarity.Developmental biology · 2014Article
- Source-dependent intracellular distribution of iron in lens epithelial cells cultured under normoxic and hypoxic conditions.Investigative ophthalmology & visual science · 2013Article
- Regulation of mouse lens maturation and gene expression by Krüppel-like factor 4.Experimental eye research · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe lens grows throughout life, and lens size is a major risk factor for nuclear and cortical cataracts. A previous study showed that the hypoxic environment around the lens suppressed lens growth in older rats. The present study was conducted to investigate the mechanism responsible for the age-dependent decline in lens cell proliferation.
methodsTransgenic mice expressing Cre recombinase in the lens were bred to mice containing floxed Hif1a alleles. Transgenic mice expressing oxygen insensitive forms of HIF-1alpha in lens epithelial cells were exposed to room air or 60% oxygen. Proliferation was measured by BrdU labeling and cell death by using the TUNEL assay. Morphology was assessed in histologic sections. HIF-1alpha and p27(KIP1) levels were determined by Western blot. The expression of HIF-regulated genes was assessed on microarrays.
resultsLenses lacking Hif1a degenerated, precluding study in older animals. Breathing 60% oxygen reduced HIF-1alpha levels and HIF-1-regulated transcripts in lens epithelial cells from young and older lenses. Overexpression of oxygen-insensitive HIF-1alpha had no effect on lens size, but suppressed increased proliferation in response to oxygen. Systemic injection of the iron chelator, 1,10-phenanthroline prevented the degradation of HIF-1alpha and reduced oxygen-induced proliferation. Increasing oxygen decreased levels of p27(KIP1) in the epithelial cells of older mice, which was prevented by expressing oxygen-insensitive forms of HIF-1alpha.
conclusionsHIF-1alpha is present and HIF-1 is transcriptionally active throughout life, but suppresses growth only in older lenses. Maintaining elevated levels of p27(KIP1) in older lenses requires HIF-1. p27(KIP1) and other growth regulators may selectively suppress the proliferation of older lens epithelial cells.
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