{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:39:30Z","timestamp":1790127570782,"version":"4.0.1"},"reference-count":83,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Retina France","award":["R01 EY021505"],"award-info":[{"award-number":["R01 EY021505"]}]},{"name":"Retina France","award":["R01 EY029770"],"award-info":[{"award-number":["R01 EY029770"]}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY021505"],"award-info":[{"award-number":["R01 EY021505"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY029770"],"award-info":[{"award-number":["R01 EY029770"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cataract, the opacification of the lens, is the leading cause of blindness worldwide. Although effective, cataract surgery is costly and can lead to complications. Toward identifying alternate treatments, it is imperative to develop organoid models relevant for lens studies and drug screening. Here, we demonstrate that by culturing mouse lens epithelial cells under defined three-dimensional (3D) culture conditions, it is possible to generate organoids that display optical properties and recapitulate many aspects of lens organization and biology. These organoids can be rapidly produced in large amounts. High-throughput RNA sequencing (RNA-seq) on specific organoid regions isolated via laser capture microdissection (LCM) and immunofluorescence assays demonstrate that these lens organoids display a spatiotemporal expression of key lens genes, e.g., Jag1, Pax6, Prox1, Hsf4 and Cryab. Further, these lens organoids are amenable to the induction of opacities. Finally, the knockdown of a cataract-linked RNA-binding protein encoding gene, Celf1, induces opacities in these organoids, indicating their use in rapidly screening for genes that are functionally relevant to lens biology and cataract. In sum, this lens organoid model represents a compelling new tool to advance the understanding of lens biology and pathology and can find future use in the rapid screening of compounds aimed at preventing and\/or treating cataracts.<\/jats:p>","DOI":"10.3390\/cells12202478","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:56:57Z","timestamp":1697623017000},"page":"2478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Eye Lens Organoids Made Simple: Characterization of a New Three-Dimensional Organoid Model for Lens Development and Pathology"],"prefix":"10.3390","volume":"12","author":[{"given":"Matthieu","family":"Duot","sequence":"first","affiliation":[{"name":"CNRS, UMR 6290, Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR), Universit\u00e9 de Rennes, 35000 Rennes, France"},{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roselyne","family":"Viel","sequence":"additional","affiliation":[{"name":"CNRS, Inserm UMS Biosit, H2P2 Core Facility, Universit\u00e9 de Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Viet","sequence":"additional","affiliation":[{"name":"CNRS, UMR 6290, Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR), Universit\u00e9 de Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Le Goff-Gaillard","sequence":"additional","affiliation":[{"name":"CNRS, UMR 6290, Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR), Universit\u00e9 de Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Paillard","sequence":"additional","affiliation":[{"name":"CNRS, UMR 6290, Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR), Universit\u00e9 de Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8845-010X","authenticated-orcid":false,"given":"Salil A.","family":"Lachke","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Gautier-Courteille","sequence":"additional","affiliation":[{"name":"CNRS, UMR 6290, Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR), Universit\u00e9 de Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Reboutier","sequence":"additional","affiliation":[{"name":"CNRS, UMR 6290, Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes (IGDR), Universit\u00e9 de Rennes, 35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.tig.2017.08.001","article-title":"Signaling and Gene Regulatory Networks in Mammalian Lens Development","volume":"33","author":"Cvekl","year":"2017","journal-title":"Trends Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.preteyeres.2017.04.001","article-title":"The Lens Growth Process","volume":"60","author":"Bassnett","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1098\/rstb.2010.0302","article-title":"Biological Glass: Structural Determinants of Eye Lens Transparency","volume":"366","author":"Bassnett","year":"2011","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101112","DOI":"10.1016\/j.preteyeres.2022.101112","article-title":"The Lens Epithelium as a Major Determinant in the Development, Maintenance, and Regeneration of the Crystalline Lens","volume":"92","author":"Liu","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108662","DOI":"10.1016\/j.exer.2021.108662","article-title":"Inherited Cataracts: Genetic Mechanisms and Pathways New and Old","volume":"209","author":"Shiels","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-vision-091517-034346","article-title":"Biology of Inherited Cataracts and Opportunities for Treatment","volume":"5","author":"Shiels","year":"2019","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0140-6736(17)30544-5","article-title":"Cataracts","volume":"390","author":"Liu","year":"2017","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8459","DOI":"10.1038\/s41598-019-44676-4","article-title":"Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts","volume":"9","author":"Daszynski","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1126\/science.aac9145","article-title":"Pharmacological Chaperone for Alpha-Crystallin Partially Restores Transparency in Cataract Models","volume":"350","author":"Makley","year":"2015","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nature14650","article-title":"Lanosterol Reverses Protein Aggregation in Cataracts","volume":"523","author":"Zhao","year":"2015","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1242\/dev.02424","article-title":"AlphaA-Crystallin Expression Prevents Gamma-Crystallin Insolubility and Cataract Formation in the Zebrafish Cloche Mutant Lens","volume":"133","author":"Goishi","year":"2006","journal-title":"Development"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/dvdy.147","article-title":"Modeling Ocular Lens Disease in Xenopus","volume":"249","author":"Viet","year":"2019","journal-title":"Dev. Dyn."},{"key":"ref_13","unstructured":"Chang, C.-C. (2016). Animal Models of Ophthalmic Diseases, Springer International Publishing."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s43586-022-00174-y","article-title":"Organoids","volume":"2","author":"Zhao","year":"2022","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1167\/iovs.06-0949","article-title":"In Vitro Generation of Functional Lens-like Structures with Relevance to Age-Related Nuclear Cataract","volume":"48","author":"McAvoy","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Anchan, R.M., Lachke, S.A., Gerami-Naini, B., Lindsey, J., Ng, N., Naber, C., Nickerson, M., Cavallesco, R., Rowan, S., and Eaton, J.L. (2014). Pax6- and Six3-Mediated Induction of Lens Cell Fate in Mouse and Human ES Cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115106"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1167\/iovs.16-20504","article-title":"Generation of Functional Lentoid Bodies From Human Induced Pluripotent Stem Cells Derived From Urinary Cells","volume":"58","author":"Fu","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1096\/fj.10-157255","article-title":"Efficient Generation of Lens Progenitor Cells and Lentoid Bodies from Human Embryonic Stem Cells in Chemically Defined Conditions","volume":"24","author":"Yang","year":"2010","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"dev155838","DOI":"10.1242\/dev.155838","article-title":"Light-Focusing Human Micro-Lenses Generated from Pluripotent Stem Cells Model Lens Development and Drug-Induced Cataract in Vitro","volume":"145","author":"Murphy","year":"2018","journal-title":"Development"},{"key":"ref_20","first-page":"56","article-title":"A Human Three-Dimensional In Vitro Model of Lens Epithelial Cells as a Model to Study Mechanisms of Drug-Induced Posterior Subcapsular Cataracts","volume":"36","author":"Kustermann","year":"2019","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cvekl, A., and Camerino, M.J. (2022). Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology. Cells, 11.","DOI":"10.3390\/cells11213516"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature17181","article-title":"Lens Regeneration Using Endogenous Stem Cells with Gain of Visual Function","volume":"531","author":"Lin","year":"2016","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.exer.2014.12.011","article-title":"Molecular Characterization of Mouse Lens Epithelial Cell Lines and Their Suitability to Study RNA Granules and Cataract Associated Genes","volume":"131","author":"Terrell","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"107787","DOI":"10.1016\/j.exer.2019.107787","article-title":"Molecular Characterization of the Human Lens Epithelium-Derived Cell Line SRA01\/04","volume":"188","author":"Weatherbee","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An Efficient General Purpose Program for Assigning Sequence Reads to Genomic Features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_27","first-page":"1438","article-title":"From Reads to Genes to Pathways: Differential Expression Analysis of RNA-Seq Experiments Using Rsubread and the edgeR Quasi-Likelihood Pipeline","volume":"5","author":"Chen","year":"2016","journal-title":"F1000Research"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D875","DOI":"10.1093\/nar\/gkx837","article-title":"iSyTE 2.0: A Database for Expression-Based Gene Discovery in the Eye","volume":"46","author":"Kakrana","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.exer.2018.10.011","article-title":"Proteome-Transcriptome Analysis and Proteome Remodeling in Mouse Lens Epithelium and Fibers","volume":"179","author":"Zhao","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.exer.2018.06.004","article-title":"A Comprehensive Spatial-Temporal Transcriptomic Analysis of Differentiating Nascent Mouse Lens Epithelial and Fiber Cells","volume":"175","author":"Zhao","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.cell.2022.12.043","article-title":"Controlling Organoid Symmetry Breaking Uncovers an Excitable System Underlying Human Axial Elongation","volume":"186","author":"Anand","year":"2023","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.stem.2019.05.005","article-title":"Engineering Stem Cell Self-Organization to Build Better Organoids","volume":"24","author":"Brassard","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41586-019-1146-y","article-title":"Self-Organization and Symmetry Breaking in Intestinal Organoid Development","volume":"569","author":"Serra","year":"2019","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/bs.pmbts.2015.05.001","article-title":"Lens Development and Crystallin Gene Expression","volume":"134","author":"Cvekl","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.matbio.2020.12.005","article-title":"Dynamics of the Lens Basement Membrane Capsule and Its Interaction with Connective Tissue-like Extracapsular Matrix Proteins","volume":"96","author":"DeDreu","year":"2021","journal-title":"Matrix Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0925-4773(01)00645-1","article-title":"Prox1 Is Differentially Localized during Lens Development","volume":"112","author":"Duncan","year":"2002","journal-title":"Mech. Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e51915","DOI":"10.7554\/eLife.51915","article-title":"Etv Transcription Factors Functionally Diverge from Their Upstream FGF Signaling in Lens Development","volume":"9","author":"Garg","year":"2020","journal-title":"Elife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108682","DOI":"10.1016\/j.exer.2021.108682","article-title":"Mechanisms of Organelle Elimination for Lens Development and Differentiation","volume":"209","author":"Brennan","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.exer.2013.08.017","article-title":"Autophagy and Mitophagy Participate in Ocular Lens Organelle Degradation","volume":"116","author":"Costello","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.biocel.2016.08.022","article-title":"Heat Shock Factor 4 Regulates Lens Epithelial Cell Homeostasis by Working with Lysosome and Anti-Apoptosis Pathways","volume":"79","author":"Cui","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1242\/dev.053124","article-title":"The Ubiquitin Proteasome System Is Required for Cell Proliferation of the Lens Epithelium and for Differentiation of Lens Fiber Cells in Zebrafish","volume":"137","author":"Imai","year":"2010","journal-title":"Development"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11436","DOI":"10.1074\/jbc.M112.437103","article-title":"Deletion of Autophagy-Related 5 (Atg5) and Pik3c3 Genes in the Lens Causes Cataract Independent of Programmed Organelle Degradation","volume":"288","author":"Morishita","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6005","DOI":"10.1093\/emboj\/cdf609","article-title":"Altered Aggregation Properties of Mutant Gamma-Crystallins Cause Inherited Cataract","volume":"21","author":"Sandilands","year":"2002","journal-title":"EMBO J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.bbadis.2013.03.007","article-title":"HSF4 Regulates DLAD Expression and Promotes Lens De-Nucleation","volume":"1832","author":"Cui","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23406","DOI":"10.1038\/s41598-021-02851-6","article-title":"Comparison of Methods to Experimentally Induce Opacification and Elasticity Change in Ex Vivo Porcine Lenses","volume":"11","author":"Ruiss","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Siddam, A.D., Gautier-Courteille, C., Perez-Campos, L., Anand, D., Kakrana, A., Dang, C.A., Legagneux, V., M\u00e9reau, A., Viet, J., and Gross, J.M. (2018). The RNA-Binding Protein Celf1 Post-Transcriptionally Regulates p27Kip1 and Dnase2b to Control Fiber Cell Nuclear Degradation in Lens Development. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007278"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00439-020-02195-7","article-title":"The Cataract-Linked RNA-Binding Protein Celf1 Post-Transcriptionally Controls the Spatiotemporal Expression of the Key Homeodomain Transcription Factors Pax6 and Prox1 in Lens Development","volume":"139","author":"Aryal","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1364\/BOE.9.002176","article-title":"Non-Invasive in Vivo Quantification of the Developing Optical Properties and Graded Index of the Embryonic Eye Lens Using SPIM","volume":"9","author":"Young","year":"2018","journal-title":"Biomed. Opt. Express"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"435101","DOI":"10.1088\/1361-648X\/aae000","article-title":"Protein Refractive Index Increment Is Determined by Conformation as Well as Composition","volume":"30","author":"Khago","year":"2018","journal-title":"J. Phys. Condens. Matter"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.1038\/srep05195","article-title":"Primary Sequence Contribution to the Optical Function of the Eye Lens","volume":"4","author":"Mahendiran","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1479-7364-6-26","article-title":"The Human Crystallin Gene Families","volume":"6","author":"Wistow","year":"2012","journal-title":"Hum. Genom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.biocel.2012.02.015","article-title":"sHSP in the Eye Lens: Crystallin Mutations, Cataract and Proteostasis","volume":"44","author":"Clark","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.bbagen.2015.08.014","article-title":"Functional Sequences in Human alphaB Crystallin","volume":"1860","author":"Clark","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nourazaran, M., Yousefi, R., Moosavi-Movahedi, F., Panahi, F., Hong, J., and Moosavi-Movahedi, A.A. (2023). The Structural and Functional Consequences of Melatonin and Serotonin on Human \u03b1B-Crystallin and Their Dual Role in the Eye Lens Transparency. Biochim. Biophys. Acta (BBA)-Proteins Proteom., 1871.","DOI":"10.1016\/j.bbapap.2023.140928"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pbiomolbio.2014.02.005","article-title":"Cell Biological Roles of \u03b1B-Crystallin","volume":"115","author":"Boelens","year":"2014","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1146\/annurev-physchem-090419-121428","article-title":"\u03b1-Crystallins in the Vertebrate Eye Lens: Complex Oligomers and Molecular Chaperones","volume":"72","author":"Rocha","year":"2021","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/bs.pmbts.2015.04.007","article-title":"Lens Biology and Biochemistry","volume":"134","author":"Hejtmancik","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/978-3-642-56348-5_12","article-title":"Cytoskeletal Competence Requires Protein Chaperones","volume":"28","author":"Quinlan","year":"2002","journal-title":"Prog. Mol. Subcell. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ho, D.W.H., Yap, M.K.H., Ng, P.W., Fung, W.Y., and Yip, S.P. (2012). Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040238"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0925-4773(96)00632-6","article-title":"Ectopic Lens Induction in Fish in Response to the Murine Homeobox Gene Six3","volume":"60","author":"Oliver","year":"1996","journal-title":"Mech. Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.exer.2018.06.020","article-title":"Spatiotemporal Dynamics of Canonical Wnt Signaling during Embryonic Eye Development and Posterior Capsular Opacification (PCO)","volume":"175","author":"Wang","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.exer.2006.01.018","article-title":"Lens Epithelial Cells Synthesize and Secrete Ceruloplasmin: Effects of Ceruloplasmin and Transferrin on Iron Efflux and Intracellular Iron Dynamics","volume":"83","author":"Harned","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ydbio.2008.10.011","article-title":"Co-Operative Roles for E-Cadherin and N-Cadherin during Lens Vesicle Separation and Lens Epithelial Cell Survival","volume":"326","author":"Pontoriero","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1167\/iovs.08-2243","article-title":"Persistent FoxE3 Expression Blocks Cytoskeletal Remodeling and Organelle Degradation during Lens Fiber Differentiation","volume":"49","author":"Landgren","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.exer.2008.08.017","article-title":"On the Mechanism of Organelle Degradation in the Vertebrate Lens","volume":"88","author":"Bassnett","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ydbio.2008.06.002","article-title":"Notch Signaling Regulates Growth and Differentiation in the Mammalian Lens","volume":"321","author":"Rowan","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ydbio.2009.05.566","article-title":"Notch Signaling Is Required for Lateral Induction of Jagged1 during FGF-Induced Lens Fiber Differentiation","volume":"332","author":"Saravanamuthu","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1242\/dev.032888","article-title":"Pax6 Is Essential for Lens Fiber Cell Differentiation","volume":"136","author":"Shaham","year":"2009","journal-title":"Development"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"711","DOI":"10.3109\/02713688609015139","article-title":"Nuclear Pyknosis during Lens Fibre Differentiation in Epithelial Explants","volume":"5","author":"McAvoy","year":"1986","journal-title":"Curr. Eye Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/dgd.12128","article-title":"The Lens Equator: A Platform for Molecular Machinery That Regulates the Switch from Cell Proliferation to Differentiation in the Vertebrate Lens","volume":"56","author":"Mochizuki","year":"2014","journal-title":"Dev. Growth Differ."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.preteyeres.2012.04.002","article-title":"Pax6: A Multi-Level Regulator of Ocular Development","volume":"31","author":"Shaham","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1242\/dev.107953","article-title":"The Cellular and Molecular Mechanisms of Vertebrate Lens Development","volume":"141","author":"Cvekl","year":"2014","journal-title":"Development"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/6844","article-title":"Prox1 Function Is Crucial for Mouse Lens-Fibre Elongation","volume":"21","author":"Wigle","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_74","first-page":"318","article-title":"Prox1 and Fibroblast Growth Factor Receptors Form a Novel Regulatory Loop Controlling Lens Fiber Differentiation and Gene Expression","volume":"143","author":"Audette","year":"2016","journal-title":"Development"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/eye.2016.198","article-title":"The Zebrafish Eye-a Paradigm for Investigating Human Ocular Genetics","volume":"31","author":"Richardson","year":"2017","journal-title":"Eye"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3109\/02713689308999484","article-title":"The Prevention of Cataract Caused by Oxidative Stress in Cultured Rat Lenses. I. H2O2 and Photochemically Induced Cataract","volume":"12","author":"Spector","year":"1993","journal-title":"Curr. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1096\/fasebj.9.12.7672510","article-title":"Oxidative Stress-Induced Cataract: Mechanism of Action","volume":"9","author":"Spector","year":"1995","journal-title":"FASEB J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"108395","DOI":"10.1016\/j.exer.2020.108395","article-title":"H2O2-Induced Cataract as a Model of Age-Related Cataract: Lessons Learned from Overexpressing the Proteasome Activator PA28\u03b1\u03b2 in Mouse Eye Lens","volume":"203","author":"Hernebring","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"943","DOI":"10.3109\/02713683.2015.1080280","article-title":"Topical Use of NaCl Solution with Different Concentration Affects Lens Transparency in Anesthetized Mice","volume":"41","author":"Gu","year":"2016","journal-title":"Curr. Eye Res."},{"key":"ref_80","first-page":"559","article-title":"Reversible Cataracts in Diabetes Mellitus","volume":"65","author":"Butler","year":"1994","journal-title":"J. Am. Optom. Assoc."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/dmrr.1075","article-title":"Diabetic Cataracts: Mechanisms and Management","volume":"26","author":"Obrosova","year":"2010","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/wrna.107","article-title":"The Importance of CELF Control: Molecular and Biological Roles of the CUG-BP, Elav-like Family of RNA-Binding Proteins","volume":"3","author":"Dasgupta","year":"2012","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Siddam, A.D., Duot, M., Coomson, S.Y., Anand, D., Aryal, S., Weatherbee, B.A.T., Audic, Y., Paillard, L., and Lachke, S.A. (2023). High-Throughput Transcriptomics of Celf1 Conditional Knockout Lens Identifies Downstream Networks Linked to Cataract Pathology. Cells, 12.","DOI":"10.3390\/cells12071070"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/20\/2478\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:08:52Z","timestamp":1760130532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/20\/2478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,18]]},"references-count":83,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["cells12202478"],"URL":"https:\/\/doi.org\/10.3390\/cells12202478","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,18]]}}}