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Here, we combine the use of the nanoenvironmental sensor [6-acetyl-2-dimethylaminonaphthalene (ACDAN)] to visualize lens macromolecular crowding with in vivo studies of aquaporin 0 zebrafish mutants that disrupt its regulation. Spectral phasor analysis of ACDAN fluorescence reveals water dipolar relaxation and demonstrates that mutations in two zebrafish aquaporin 0s, Aqp0a and Aqp0b, alter water state and macromolecular crowding in living lenses. Our results provide in vivo evidence that Aqp0a promotes fluid influx in the deeper lens cortex, whereas Aqp0b facilitates fluid efflux. This evidence reveals previously unidentified spatial regulation of macromolecular crowding and spatially distinct roles for Aqp0 in the lens.<\/jats:p>","DOI":"10.1126\/sciadv.abj4833","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T13:51:30Z","timestamp":1645019490000},"source":"Crossref","is-referenced-by-count":29,"title":["In vivo macromolecular crowding is differentially modulated by aquaporin 0 in zebrafish lens: Insights from a nanoenvironment sensor and spectral imaging"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3793-9201","authenticated-orcid":true,"given":"Irene","family":"Vorontsova","sequence":"first","affiliation":[{"name":"Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA."},{"name":"Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA."},{"name":"Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7149-9385","authenticated-orcid":true,"given":"Alexander","family":"Vallmitjana","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of California, Irvine, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-3422","authenticated-orcid":true,"given":"Bel\u00e9n","family":"Torrado","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of California, Irvine, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-8695","authenticated-orcid":true,"given":"Thomas F.","family":"Schilling","sequence":"additional","affiliation":[{"name":"Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6450-7391","authenticated-orcid":true,"given":"Enrico","family":"Gratton","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of California, Irvine, Irvine, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-9229","authenticated-orcid":true,"given":"Leonel","family":"Malacrida","sequence":"additional","affiliation":[{"name":"Departamento de Fisiopatolog\u00eda, Hospital de Cl\u00ednicas, Facultad de Medicina, Universidad de la Rep\u00fablica, Montevideo, Uruguay."},{"name":"Advanced Bioimaging Unit, Institut Pasteur of Montevideo and Universidad de la Rep\u00fablica, Montevideo, Uruguay."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2620"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18933-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41567-020-0957-y"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.10.051"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165908"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.09.012"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0433-z"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.57.070188.002403"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2016.09.002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-007-9019-y"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1985.249.3.C181"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.05.011"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00214.2017"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122693"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.9b00106"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.10.103"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2016.1217547"},{"key":"e_1_3_3_19_2","first-page":"3191","article-title":"The effect of the interaction between aquaporin 0 (AQP0) and the filensin tail region on AQP0 water permeability","volume":"17","author":"Nakazawa Y.","year":"2011","unstructured":"Y. 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