ArticleInvestigative ophthalmology & visual science2019
The Connexin50D47A Mutant Causes Cataracts by Calcium Precipitation.
Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Extrinsic Modulation of the Zonular Tension Induces Calcium Influx in Lens Fiber Cells That Is Mediated by Mechanosensitive TRPV1 and TRPV4 Channels.Investigative ophthalmology & visual science · 2026Article
- Preventing Age-Related Nuclear Cataract Development - Is Cholesterol the Key?Investigative ophthalmology & visual science · 2026Review
- Regional Differences in Calcium Dynamics in the Intact Lens: The Role of TRPV Channels in Lens Calcium Regulation.Investigative ophthalmology & visual science · 2025Article
- Calcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions.bioRxiv : the preprint server for biology · 2025Article
- The rectification of heterotypic Cx46/Cx50 gap junction channels depends on intracellular magnesium.Biophysics reports · 2024Article
- Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon?Antioxidants (Basel, Switzerland) · 2024Review
- Longitudinal study of microphthalmia in connexin 50 knockout mice using spectral-domain optical coherence tomography.Frontiers in ophthalmology · 2024Article
- Charged multivesicular body protein 4b forms complexes with gap junction proteins during lens fiber cell differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Pediatric cataracts of different etiologies contain insoluble, calcified particles.Frontiers in ophthalmology · 2023Article
- Levels and Modifications of Both Lens Fiber Cell Connexins Are Affected in Connexin Mutant Mice.Cells · 2022Article
- Connexin Mutants Cause Cataracts Through Deposition of Apatite.Frontiers in cell and developmental biology · 2022Article
- Loss of fiber cell communication may contribute to the development of cataracts of many different etiologies.Frontiers in physiology · 2022Review
- Mutations of CX46/CX50 and Cataract Development.Frontiers in molecular biosciences · 2022Review
- Molecular mechanisms underlying enhanced hemichannel function of a cataract-associated Cx50 mutant.Biophysical journal · 2021Article
- Quantitative X-ray tomographic analysis reveals calcium precipitation in cataractogenesis.Scientific reports · 2021Article
- Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis.Antioxidants (Basel, Switzerland) · 2021Review
- Do Connexin Mutants Cause Cataracts by Perturbing Glutathione Levels and Redox Metabolism in the Lens?Biomolecules · 2020Article
- Connexin Mutants Compromise the Lens Circulation and Cause Cataracts through Biomineralization.International journal of molecular sciences · 2020Review
- Connexin 50-R205G Mutation Perturbs Lens Epithelial Cell Proliferation and Differentiation.Investigative ophthalmology & visual science · 2020Article
- p62/Sequestosome 1 levels increase and phosphorylation is altered in Cx50D47A lenses, but deletion of p62/sequestosome 1 does not improve transparency.Molecular vision · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: Mutations in connexin50 (Cx50) and connexin46 (Cx46) cause cataracts. Because the expression of Cx46fs380 leads to decreased gap junctional coupling and formation of calcium precipitates, we studied Cx50D47A lenses to test whether Cx50 mutants also cause cataracts due to calcium precipitation. Methods: Connexin levels were determined by immunoblotting. Gap junctional coupling conductance was calculated from intracellular impedance studies of intact lenses. Intracellular hydrostatic pressure was measured using a microelectrode/manometer system. Intracellular free calcium ion concentrations ([Ca2+]i) were measured using Fura-2 and fluorescence imaging. Calcium precipitation was assessed by Alizarin red staining and compared to the distribution of opacities in darkfield images. Results: In Cx50D47A lenses, Cx50 levels were 11% (heterozygotes) and 1.2% (homozygotes), and Cx46 levels were 52% (heterozygotes) and 30% (homozygotes) when compared to wild-type at 2.5 months. Gap junctional coupling in differentiating fibers of Cx50D47A lenses was 49% (heterozygotes) and 29% (homozygotes), and in mature fibers, it was 24% (heterozygotes) and 4% (homozygotes) compared to wild-type lenses. Hydrostatic pressure was significantly increased in Cx50D47A lenses. [Ca2+]i was significantly increased in Cx50D47A lenses. Alizarin red-stained calcium precipitates were present in homozygous Cx50D47A lenses with a similar distribution to the cataracts. Conclusions: Cx50D47A expression altered the lens internal circulation by decreasing connexin levels and gap junctional coupling. Reduced water and ion outflow through gap junctions increased the gradients of intracellular hydrostatic pressure and concentrations of free calcium ions. In these lenses, calcium ions accumulated, precipitated, and formed cataracts. These results suggest that mutant lens fiber connexins lead to calcium precipitates, which may cause cataracts.
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