{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T04:54:10Z","timestamp":1771995250662,"version":"3.50.1"},"reference-count":94,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NEI","award":["EY028899"],"award-info":[{"award-number":["EY028899"]}]},{"name":"NIH\/NEI","award":["EY02687"],"award-info":[{"award-number":["EY02687"]}]},{"name":"NIH\/NEI","award":["NS103350"],"award-info":[{"award-number":["NS103350"]}]},{"name":"NIH\/NEI","award":["EY009532"],"award-info":[{"award-number":["EY009532"]}]},{"name":"NIH\/NEI","award":["EY029171"],"award-info":[{"award-number":["EY029171"]}]},{"name":"NIH\/NEI","award":["P30 CA91842"],"award-info":[{"award-number":["P30 CA91842"]}]},{"name":"NIH\/NEI","award":["UL1TR002345"],"award-info":[{"award-number":["UL1TR002345"]}]},{"name":"Department of Ophthalmology and Visual Sciences as well as a Career Development Award","award":["EY028899"],"award-info":[{"award-number":["EY028899"]}]},{"name":"Department of Ophthalmology and Visual Sciences as well as a Career Development Award","award":["EY02687"],"award-info":[{"award-number":["EY02687"]}]},{"name":"Department of Ophthalmology and Visual Sciences as well as a Career Development Award","award":["NS103350"],"award-info":[{"award-number":["NS103350"]}]},{"name":"Department of Ophthalmology and Visual Sciences as well as a Career Development Award","award":["EY009532"],"award-info":[{"award-number":["EY009532"]}]},{"name":"Department of Ophthalmology and Visual Sciences as well as a Career Development Award","award":["EY029171"],"award-info":[{"award-number":["EY029171"]}]},{"name":"Department of Ophthalmology and Visual Sciences as well as a Career Development Award","award":["P30 CA91842"],"award-info":[{"award-number":["P30 CA91842"]}]},{"name":"Department of Ophthalmology and Visual Sciences as well as a Career Development Award","award":["UL1TR002345"],"award-info":[{"award-number":["UL1TR002345"]}]},{"name":"NIH","award":["EY028899"],"award-info":[{"award-number":["EY028899"]}]},{"name":"NIH","award":["EY02687"],"award-info":[{"award-number":["EY02687"]}]},{"name":"NIH","award":["NS103350"],"award-info":[{"award-number":["NS103350"]}]},{"name":"NIH","award":["EY009532"],"award-info":[{"award-number":["EY009532"]}]},{"name":"NIH","award":["EY029171"],"award-info":[{"award-number":["EY029171"]}]},{"name":"NIH","award":["P30 CA91842"],"award-info":[{"award-number":["P30 CA91842"]}]},{"name":"NIH","award":["UL1TR002345"],"award-info":[{"award-number":["UL1TR002345"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>TRPM3 belongs to the melastatin sub-family of transient receptor potential (TRPM) cation channels and has been shown to function as a steroid-activated, heat-sensitive calcium ion (Ca2+) channel. A missense substitution (p.I65M) in the TRPM3 gene of humans (TRPM3) and mice (Trpm3) has been shown to underlie an inherited form of early-onset, progressive cataract. Here, we model the pathogenetic effects of this cataract-causing mutation using \u2018knock-in\u2019 mutant mice and human cell lines. Trpm3 and its intron-hosted micro-RNA gene (Mir204) were strongly co-expressed in the lens epithelium and other non-pigmented and pigmented ocular epithelia. Homozygous Trpm3-mutant lenses displayed elevated cytosolic Ca2+ levels and an imbalance of sodium (Na+) and potassium (K+) ions coupled with increased water content. Homozygous TRPM3-mutant human lens epithelial (HLE-B3) cell lines and Trpm3-mutant lenses exhibited increased levels of phosphorylated mitogen-activated protein kinase 1\/extracellular signal-regulated kinase 2 (MAPK1\/ERK2\/p42) and MAPK3\/ERK1\/p44. Mutant TRPM3-M65 channels displayed an increased sensitivity to external Ca2+ concentration and an altered dose response to pregnenolone sulfate (PS) activation. Trpm3-mutant lenses shared the downregulation of genes involved in insulin\/peptide secretion and the upregulation of genes involved in Ca2+ dynamics. By contrast, Trpm3-deficient lenses did not replicate the pathophysiological changes observed in Trpm3-mutant lenses. Collectively, our data suggest that a cataract-causing substitution in the TRPM3 cation channel elicits a deleterious gain-of-function rather than a loss-of-function mechanism in the lens.<\/jats:p>","DOI":"10.3390\/cells13030257","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T03:45:12Z","timestamp":1706586312000},"page":"257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8517-1292","authenticated-orcid":false,"given":"Yuefang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8867-1110","authenticated-orcid":false,"given":"Thomas M.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3520-6407","authenticated-orcid":false,"given":"Philip A.","family":"Ruzycki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-5688","authenticated-orcid":false,"given":"Zhaohua","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Qing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-4242","authenticated-orcid":false,"given":"Mohammad","family":"Shahidullah","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-1645","authenticated-orcid":false,"given":"Nicholas A.","family":"Delamere","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4610-596X","authenticated-orcid":false,"given":"Alan","family":"Shiels","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature02196","article-title":"TRP channels as cellular sensors","volume":"426","author":"Clapham","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3109\/01677063.2010.514369","article-title":"The history of the Drosophila TRP channel: The birth of a new channel superfamily","volume":"24","author":"Minke","year":"2010","journal-title":"J. Neurogenet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/cphy.c110026","article-title":"TRP channels","volume":"2","author":"Gees","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1124\/pr.113.008268","article-title":"Transient receptor potential channels as drug targets: From the science of basic research to the art of medicine","volume":"66","author":"Nilius","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"jcs258372","DOI":"10.1242\/jcs.258372","article-title":"TRP channels in health and disease at a glance","volume":"134","author":"Yue","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/978-3-642-54215-2_15","article-title":"Trpm1","volume":"222","author":"Irie","year":"2014","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/j.1600-0625.2012.01565.x","article-title":"Role of TRPM in melanocytes and melanoma","volume":"21","author":"Guo","year":"2012","journal-title":"Exp. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.preteyeres.2014.09.001","article-title":"Congenital stationary night blindness: An analysis and update of genotype-phenotype correlations and pathogenic mechanisms","volume":"45","author":"Zeitz","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1001\/jamaophthalmol.2018.0185","article-title":"Presentation of TRPM1-Associated Congenital Stationary Night Blindness in Children","volume":"136","author":"Pfeifer","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1332","DOI":"10.1111\/aos.15186","article-title":"Clinical and genetic findings in TRPM1-related congenital stationary night blindness","volume":"100","author":"Iosifidis","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bellone, R.R., Holl, H., Setaluri, V., Devi, S., Maddodi, N., Archer, S., Sandmeyer, L., Ludwig, A., Foerster, D., and Pruvost, M. (2013). Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078280"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22540","DOI":"10.1074\/jbc.M503092200","article-title":"Alternative splicing switches the divalent cation selectivity of TRPM3 channels","volume":"280","author":"Oberwinkler","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"36663","DOI":"10.1074\/jbc.M112.396663","article-title":"Alternative splicing of a protein domain indispensable for function of transient receptor potential melastatin 3 (TRPM3) ion channels","volume":"287","author":"Fruhwald","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00424-010-0838-9","article-title":"TRPM3 channels provide a regulated influx pathway for zinc in pancreatic beta cells","volume":"460","author":"Wagner","year":"2010","journal-title":"Pflugers Arch."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/nchembio.1428","article-title":"Opening of an alternative ion permeation pathway in a nociceptor TRP channel","volume":"10","author":"Vriens","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4161\/23328940.2014.988524","article-title":"TRPM3 in temperature sensing and beyond","volume":"2","author":"Held","year":"2015","journal-title":"Temperature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1113\/JP274124","article-title":"Mutations in the voltage-sensing domain affect the alternative ion permeation pathway in the TRPM3 channel","volume":"596","author":"Held","year":"2018","journal-title":"J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/978-3-540-34891-7_15","article-title":"Trpm3","volume":"179","author":"Oberwinkler","year":"2007","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/978-3-642-54215-2_17","article-title":"Trpm3","volume":"222","author":"Oberwinkler","year":"2014","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1124\/pr.57.4.13","article-title":"Overview of molecular relationships in the voltage-gated ion channel superfamily","volume":"57","author":"Yu","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ceca.2018.03.005","article-title":"Ca(2+)-dependent regulation and binding of calmodulin to multiple sites of Transient Receptor Potential Melastatin 3 (TRPM3) ion channels","volume":"73","author":"Przibilla","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.neuron.2022.10.002","article-title":"Structural and functional analyses of a GPCR-inhibited ion channel TRPM3","volume":"111","author":"Zhao","year":"2023","journal-title":"Neuron"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21493","DOI":"10.1074\/jbc.M300945200","article-title":"Molecular and functional characterization of the melastatin-related cation channel TRPM3","volume":"278","author":"Grimm","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/ncb1801","article-title":"Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells","volume":"10","author":"Wagner","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E1363","DOI":"10.1073\/pnas.1419845112","article-title":"Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release","volume":"112","author":"Held","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1085\/jgp.201411339","article-title":"Regulation of the transient receptor potential channel TRPM3 by phosphoinositides","volume":"146","author":"Toth","year":"2015","journal-title":"J. Gen. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1085\/jgp.201411336","article-title":"Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel","volume":"146","author":"Badheka","year":"2015","journal-title":"J. Gen. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1111\/bph.14812","article-title":"Heat sensing involves a TRiPlet of ion channels","volume":"176","author":"Vriens","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Persoons, E., Kerselaers, S., Voets, T., Vriens, J., and Held, K. (2021). Partial Agonistic Actions of Sex Hormone Steroids on TRPM3 Function. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413652"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1111\/bph.12524","article-title":"Activation and inhibition of transient receptor potential TRPM3-induced gene transcription","volume":"171","author":"Lesch","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1124\/mol.114.095695","article-title":"Transient receptor potential melastatin-3 (TRPM3)-induced activation of AP-1 requires Ca2+ ions and the transcription factors c-Jun, ATF2, and ternary complex factor","volume":"87","author":"Lesch","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1002\/jcb.25904","article-title":"Extracellular Signal-Regulated Protein Kinase, c-Jun N-terminal Protein Kinase, and Calcineurin Regulate Transient Receptor Potential M3 (TRPM3) Induced Activation of AP-1","volume":"118","author":"Lesch","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.phrs.2017.07.014","article-title":"Transient receptor potential TRPM3 channels: Pharmacology, signaling, and biological functions","volume":"124","author":"Thiel","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Thiel, G., and Rossler, O.G. (2022). TRPM3-Induced Gene Transcription Is under Epigenetic Control. Pharmaceuticals, 15.","DOI":"10.3390\/ph15070846"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Thiel, G., and Rossler, O.G. (2023). Calmodulin Regulates Transient Receptor Potential TRPM3 and TRPM8-Induced Gene Transcription. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097902"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1124\/mol.113.086843","article-title":"Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivo","volume":"84","author":"Straub","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1097\/j.pain.0000000000000846","article-title":"Primidone inhibits TRPM3 and attenuates thermal nociception in vivo","volume":"158","author":"Krugel","year":"2017","journal-title":"Pain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e26147","DOI":"10.7554\/eLife.26147","article-title":"Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein betagamma subunits","volume":"6","author":"Badheka","year":"2017","journal-title":"eLife"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e26280","DOI":"10.7554\/eLife.26280","article-title":"Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels","volume":"6","author":"Dembla","year":"2017","journal-title":"eLife"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e26138","DOI":"10.7554\/eLife.26138","article-title":"G protein betagamma subunits inhibit TRPM3 ion channels in sensory neurons","volume":"6","author":"Quallo","year":"2017","journal-title":"eLife"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kelemen, B., Lisztes, E., Vladar, A., Hanyicska, M., Almassy, J., Olah, A., Szollosi, A.G., Penzes, Z., Posta, J., and Voets, T. (2020). Volatile anaesthetics inhibit the thermosensitive nociceptor ion channel transient receptor potential melastatin 3 (TRPM3). Biochem. Pharmacol., 174.","DOI":"10.1016\/j.bcp.2020.113826"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ccell.2014.09.015","article-title":"TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma","volume":"26","author":"Hall","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1515\/hsz-2018-0455","article-title":"Transient receptor potential channels in the context of nociception and pain-recent insights into TRPM3 properties and function","volume":"400","author":"Behrendt","year":"2019","journal-title":"Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.33594\/000000304","article-title":"Control of Insulin Release by Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels","volume":"54","author":"Becker","year":"2020","journal-title":"Cell Physiol. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E7212","DOI":"10.1073\/pnas.1800455115","article-title":"Genetic selection of athletic success in sport-hunting dogs","volume":"115","author":"Kim","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/jhg.2009.30","article-title":"Molecular karyotyping in 17 patients and mutation screening in 41 patients with Kabuki syndrome","volume":"54","author":"Kuniba","year":"2009","journal-title":"J. Hum. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s11689-011-9076-5","article-title":"A family with autism and rare copy number variants disrupting the Duchenne\/Becker muscular dystrophy gene DMD and TRPM3","volume":"3","author":"Pagnamenta","year":"2011","journal-title":"J. Neurodev. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/ced.14883","article-title":"A novel candidate gene in autosomal dominant facial pruritus","volume":"47","author":"Thompson","year":"2022","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1002\/ajmg.a.62673","article-title":"Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia","volume":"188","author":"Lines","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_50","unstructured":"Adam, M.P., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (2023). GeneReviews((R)), NCBI."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e81032","DOI":"10.7554\/eLife.81032","article-title":"Gain-of-function variants in the ion channel gene TRPM3 underlie a spectrum of neurodevelopmental disorders","volume":"12","author":"Burglen","year":"2023","journal-title":"eLife"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bennett, T.M., Mackay, D.S., Siegfried, C.J., and Shiels, A. (2014). Mutation of the melastatin-related cation channel, TRPM3, underlies inherited cataract and glaucoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104000"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13023-018-0828-0","article-title":"Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract","volume":"13","author":"Li","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40246-020-00258-4","article-title":"TRPM3_miR-204: A complex locus for eye development and disease","volume":"14","author":"Shiels","year":"2020","journal-title":"Hum. Genom."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Yonova-Doing, E., Zhao, W., Igo, R.P., Wang, C., Sundaresan, P., Lee, K.E., Jun, G.R., Alves, A.C., Chai, X., and Chan, A.S.Y. (2020). Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-01421-2"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41586-021-03855-y","article-title":"Rare variant contribution to human disease in 281,104 UK Biobank exomes","volume":"597","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.gendis.2021.02.009","article-title":"Age-related macular degeneration: Epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy","volume":"9","author":"Deng","year":"2022","journal-title":"Genes. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15871","DOI":"10.1038\/s41598-023-43072-3","article-title":"Mechanosensitive ion channel gene survey suggests potential roles in primary open angle glaucoma","volume":"13","author":"Liu","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E3236","DOI":"10.1073\/pnas.1401464112","article-title":"MiR-204 is responsible for inherited retinal dystrophy associated with ocular coloboma","volume":"112","author":"Conte","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1006\/dbio.2000.9638","article-title":"The lens organizes the anterior segment: Specification of neural crest cell differentiation in the avian eye","volume":"220","author":"Beebe","year":"2000","journal-title":"Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.preteyeres.2015.02.002","article-title":"Crystalline lens and refractive development","volume":"47","author":"Iribarren","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_62","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_63","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.preteyeres.2016.09.002","article-title":"The physiological optics of the lens","volume":"56","author":"Donaldson","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_64","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_65","doi-asserted-by":"crossref","unstructured":"Shaham, O., Gueta, K., Mor, E., Oren-Giladi, P., Grinberg, D., Xie, Q., Cvekl, A., Shomron, N., Davis, N., and Keydar-Prizant, M. (2013). Pax6 regulates gene expression in the vertebrate lens through miR-204. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003357"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1460-9568.2011.07944.x","article-title":"Profound defects in pupillary responses to light in TRPM-channel null mice: A role for TRPM channels in non-image-forming photoreception","volume":"35","author":"Hughes","year":"2012","journal-title":"Eur. J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1093\/hmg\/ddz171","article-title":"Regulation of phagolysosomal activity by miR-204 critically influences structure and function of retinal pigment epithelium\/retina","volume":"28","author":"Zhang","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","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-fibrotic and immune cell responses","volume":"35","author":"Zhou","year":"2021","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.neuron.2015.02.022","article-title":"Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance","volume":"85","author":"Madisen","year":"2015","journal-title":"Neuron"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.neuron.2011.02.051","article-title":"TRPM3 is a nociceptor channel involved in the detection of noxious heat","volume":"70","author":"Vriens","year":"2011","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1167\/iovs.03-0856","article-title":"Insertion of a Pax6 consensus binding site into the alphaA-crystallin promoter acts as a lens epithelial cell enhancer in transgenic mice","volume":"45","author":"Zhao","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.1167\/iovs.06-0423","article-title":"Inbred FVB\/N mice are mutant at the cp49\/Bfsp2 locus and lack beaded filament proteins in the lens","volume":"47","author":"Simirskii","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diff.2018.05.002","article-title":"Epha2 and Efna5 participate in lens cell pattern-formation","volume":"102","author":"Zhou","year":"2018","journal-title":"Differentiation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.bbadis.2016.05.003","article-title":"Lens ER-stress response during cataract development in Mip-mutant mice","volume":"1862","author":"Zhou","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.diff.2019.07.003","article-title":"A charged multivesicular body protein (CHMP4B) is required for lens growth and differentiation","volume":"109","author":"Zhou","year":"2019","journal-title":"Differentiation"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Bennett, T.M., Ruzycki, P.A., and Shiels, A. (2021). Mutation of the EPHA2 Tyrosine-Kinase Domain Dysregulates Cell Pattern Formation and Cytoskeletal Gene Expression in the Lens. Cells, 10.","DOI":"10.3390\/cells10102606"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e22801","DOI":"10.1096\/fj.202201368RR","article-title":"Charged multivesicular body protein 4b forms complexes with gap junction proteins during lens fiber cell differentiation","volume":"37","author":"Zhou","year":"2023","journal-title":"FASEB J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"C465","DOI":"10.1152\/ajpcell.1996.270.2.C465","article-title":"Influence of amphotericin B on the sodium pump of porcine lens epithelium","volume":"270","author":"Delamere","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0014-4835(76)90047-6","article-title":"The effects of hyperosmotic agents on the electrical properties of the amphibian lens in vitro","volume":"22","author":"Yorio","year":"1976","journal-title":"Exp. Eye Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1097\/j.pain.0000000000002147","article-title":"Increase in trigeminal ganglion neurons that respond to both calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide in mouse models of chronic migraine and posttraumatic headache","volume":"162","author":"Guo","year":"2021","journal-title":"Pain"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1038\/s41467-019-10753-5","article-title":"The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression","volume":"10","author":"Huang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature12354","article-title":"Ultrasensitive fluorescent proteins for imaging neuronal activity","volume":"499","author":"Chen","year":"2013","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"20890","DOI":"10.1074\/jbc.M211232200","article-title":"Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3)","volume":"278","author":"Lee","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_89","first-page":"603","article-title":"CP49 and filensin intermediate filaments are essential for formation of cold cataract","volume":"26","author":"Li","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.exer.2008.10.025","article-title":"The mechanisms of calcium homeostasis and signalling in the lens","volume":"88","author":"Rhodes","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1146\/annurev.biochem.71.102201.141218","article-title":"Biochemistry of Na,K-ATPase","volume":"71","author":"Kaplan","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.biophys.093008.131331","article-title":"P-type ATPases","volume":"40","author":"Palmgren","year":"2011","journal-title":"Annu. Rev. Biophys."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Nakazawa, Y., Doki, Y., Sugiyama, Y., Kobayashi, R., Nagai, N., Morisita, N., Endo, S., Funakoshi-Tago, M., and Tamura, H. (2021). Effect of Alpha-Glucosyl-Hesperidin Consumption on Lens Sclerosis and Presbyopia. Cells, 10.","DOI":"10.3390\/cells10020382"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3892\/mmr.2023.12990","article-title":"Hesperetin treatment attenuates glycation of lens proteins and advanced-glycation end products generation","volume":"27","author":"Doki","year":"2023","journal-title":"Mol. Med. Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/3\/257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:51:33Z","timestamp":1760104293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/3\/257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":94,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["cells13030257"],"URL":"https:\/\/doi.org\/10.3390\/cells13030257","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,30]]}}}