{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:22:05Z","timestamp":1778019725132,"version":"3.51.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Cataracts are lens opacities that are among the most common causes of blindness. It is commonly believed that cataracts develop through the accumulation of damage to lens proteins. However, recent evidence suggests that cataracts can result from calcium ion accumulation and the precipitation of calcium-containing salts. To test for the presence of precipitates and to identify their components, we studied the lenses of mice that develop cataracts due to mutations of connexin46 and connexin50. Micro-computed tomography showed the presence of radio-dense mineral in the mutant lenses, but not in wild-type lenses. Three-dimensional reconstructions of the scans showed that the distribution of the radio-dense mineral closely paralleled the location and morphology of the cataracts. The mutant lens homogenates also contained insoluble particles that stained with Alizarin red (a dye that stains Ca<jats:sup>2+<\/jats:sup> deposits). Using attenuated total internal reflection micro\u2013Fourier transform infrared spectroscopy, we identified the mineral as calcium phosphate in the form of apatite. Taken together, these data support the novel paradigm that cataracts are formed through pathological mineralization within the lens.<\/jats:p>","DOI":"10.3389\/fcell.2022.951231","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T15:22:12Z","timestamp":1658503332000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Connexin Mutants Cause Cataracts Through Deposition of Apatite"],"prefix":"10.3389","volume":"10","author":[{"given":"Peter J.","family":"Minogue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre J.","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"James C.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon B.","family":"Bledsoe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric C.","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana M.","family":"Berthoud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1118\/1.2207135","article-title":"X\u2010Ray Imaging in Advanced Studies of Ophthalmic Diseases","volume":"33","author":"Antunes","year":"2006","journal-title":"Med. Phys."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1167\/iovs.18-26459","article-title":"The Connexin50D47A Mutant Causes Cataracts by Calcium Precipitation","volume":"60","author":"Berthoud","year":"2019","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"7614","DOI":"10.1167\/iovs.13-13188","article-title":"Connexin50D47A Decreases Levels of Fiber Cell Connexins and Impairs Lens Fiber Cell Differentiation","volume":"54","author":"Berthoud","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6639","DOI":"10.1167\/iovs.14-15012","article-title":"Connexin46fs380 Causes Progressive Cataracts","volume":"55","author":"Berthoud","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B5","first-page":"50","author":"Beyer","year":"2019"},{"key":"B6","first-page":"265","article-title":"Morgagnian Cataract","volume":"96","author":"Bron","year":"1976","journal-title":"Trans. Ophthalmol. Soc. U. K."},{"key":"B7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/j.1365-2818.2005.01491.x","article-title":"Calcification of Senile Cataractous Lens Determined by Fourier Transform Infrared (FTIR) and Raman Microspectroscopies","volume":"219","author":"Chen","year":"2005","journal-title":"J. Microsc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/9780470720875.ch8","article-title":"Calcium and the Physiology of Cataract","volume":"106","author":"Duncan","year":"1984","journal-title":"Ciba Found. Symp."},{"key":"B9","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0014-4835(77)90130-0","article-title":"Distribution of Non-Diffusible Calcium and Sodium in Normal and Cataractous Human Lenses","volume":"25","author":"Duncan","year":"1977","journal-title":"Exp. Eye Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/0014-4835(86)90074-6","article-title":"Human and Experimental Lens Repair and Calcification","volume":"43","author":"Fagerholm","year":"1986","journal-title":"Exp. Eye Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3109\/02713688109001866","article-title":"Calcification in the Human Lens","volume":"1","author":"Fagerholm","year":"1982","journal-title":"Curr. Eye Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/0027-5107(83)90153-7","article-title":"A Comparison of the Dominant Cataract and Recessive Specific-Locus Mutation Rates Induced by Treatment of Male Mice with Ethylnitrosourea","volume":"110","author":"Favor","year":"1983","journal-title":"Mutat. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.mri.2012.05.001","article-title":"3D Slicer as an Image Computing Platform for the Quantitative Imaging Network","volume":"30","author":"Fedorov","year":"2012","journal-title":"Magn. Reson. Imaging"},{"key":"B14","doi-asserted-by":"publisher","first-page":"C492","DOI":"10.1152\/ajpcell.00277.2017","article-title":"Disruption of the Lens Circulation Causes Calcium Accumulation and Precipitates in Connexin Mutant Mice","volume":"314","author":"Gao","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1085\/jgp.200409121","article-title":"Connections Between Connexins, Calcium, and Cataracts in the Lens","volume":"124","author":"Gao","year":"2004","journal-title":"J. Gen. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1366\/000370210792966161","article-title":"The Advantages of an Attenuated Total Internal Reflection Infrared Microspectroscopic Imaging Approach for Kidney Biopsy Analysis","volume":"64","author":"Gulley-Stahl","year":"2010","journal-title":"Appl. Spectrosc."},{"key":"B17","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/0014-4835(82)90087-2","article-title":"Calcium Content and Distribution in Human Cataract","volume":"34","author":"Hightower","year":"1982","journal-title":"Exp. Eye Res."},{"key":"B18","first-page":"1","volume-title":"Cataract. Structure of the Lens and the Nature of Its Opacity. On Cataract, and the Operation of Its Removal by Absorption With the Fine Needle Through the Cornea","author":"Jacob","year":"1851"},{"key":"B19","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1007\/s003920170032","article-title":"Formation and Transformation of Calcium Phosphates: Relevance to Vascular Calcification","volume":"90","author":"LeGeros","year":"2001","journal-title":"Z. Kardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e12624","DOI":"10.1371\/journal.pone.0012624","article-title":"Connexin Mediated Cataract Prevention in Mice","volume":"5","author":"Li","year":"2010","journal-title":"PLoS ONE"},{"key":"B21","doi-asserted-by":"publisher","first-page":"17401","DOI":"10.1038\/s41598-021-96867-7","article-title":"Quantitative X-Ray Tomographic Analysis Reveals Calcium Precipitation in Cataractogenesis","volume":"11","author":"Li","year":"2021","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1073\/pnas.1404059112","article-title":"Altered Ubiquitin Causes Perturbed Calcium Homeostasis, Hyperactivation of Calpain, Dysregulated Differentiation, and Cataract","volume":"112","author":"Liu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00232-007-9019-y","article-title":"The Lens Circulation","volume":"216","author":"Mathias","year":"2007","journal-title":"J. Membr. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4366","DOI":"10.1167\/iovs.17-21684","article-title":"Physiological and Optical Alterations Precede the Appearance of Cataracts in Cx46fs380 Mice","volume":"58","author":"Minogue","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1055\/s-2008-1054431","article-title":"Die Sph\u00e4rolithen der Linse","volume":"184","author":"Pau","year":"1984","journal-title":"Klin. Monatsbl. Augenheilkd."},{"key":"B26","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1590\/S0042-96862004001100009","article-title":"Global Data on Visual Impairment in the Year 2002","volume":"82","author":"Resnikoff","year":"2004","journal-title":"Bull. World Health Organ."},{"key":"B27","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s00240-007-0131-3","article-title":"The Future of Stone Research: Rummagings in the Attic, Randall's Plaque, Nanobacteria, and Lessons from Phylogeny","volume":"36","author":"Ryall","year":"2008","journal-title":"Urol. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An Open-Source Platform for Biological-Image Analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1016\/j.bbagen.2009.05.008","article-title":"Lens Aging: Effects of Crystallins","volume":"1790","author":"Sharma","year":"2009","journal-title":"Biochim. Biophys. Acta."},{"key":"B30","doi-asserted-by":"publisher","first-page":"5007","DOI":"10.1167\/iovs.19-27535","article-title":"Molecular Processes Implicated in Human Age-Related Nuclear Cataract","volume":"60","author":"Truscott","year":"2019","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5802\/crchim.89","article-title":"Using Micro Computed Tomographic Imaging for Analyzing Kidney Stones","volume":"24","author":"Williams","year":"2021","journal-title":"C. R. Chim."},{"key":"B32","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1267\/ahc.2.83","article-title":"Histochemical Identification of Calcium Oxalate","volume":"2","author":"Yasue","year":"1969","journal-title":"Acta Histochem. Cytochem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e21288","DOI":"10.1096\/fj.202002037R","article-title":"Mutation of the TRPM3 Cation Channel Underlies Progressive Cataract Development and Lens Calcification Associated with Pro\u2010Fibrotic and Immune Cell Responses","volume":"35","author":"Zhou","year":"2021","journal-title":"FASEB J."},{"key":"B34","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1001\/archopht.1958.00940080388005","article-title":"Calcium Oxalate Crystals Within Ocular Tissues. A Clinicopathologic and Histochemical Study","volume":"60","author":"Zimmerman","year":"1958","journal-title":"AMA Arch. Ophthalmol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.951231\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T15:22:19Z","timestamp":1658503339000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.951231\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":34,"alternative-id":["10.3389\/fcell.2022.951231"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.951231","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"article-number":"951231"}}