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In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), dysmorphic traits like cell enlargement and apparent multinucleation emerge. Multinucleation has been hypothesized to result from cellular fusion, a compensatory mechanism to maintain cell-to-cell contact and barrier function, as well as conserve resources in unhealthy tissue. However, traditional two-dimensional (2D) imaging using apical border markers alone may misrepresent multinucleation due to the lack of lateral markers. We present high-resolution confocal images enabling three-dimensional (3D) visualization of apical (ZO-1) and lateral (\u03b1-catenin) markers alongside nuclei. In two RPE damage models, we find that seemingly multinucleated cells are often single cells with displaced neighboring nuclei and lateral membranes. This emphasizes the need for 3D analyses to avoid misidentifying multinucleation and underlying fusion mechanisms. Lastly, images from the NaIO3 oxidative damage model reveal variability in RPE damage, with elongated, dysmorphic cells showing increased ZsGreen reporter protein expression driven by EMT-linked CAG promoter activity, while more regular RPE cells displayed somewhat reduced green signal more typical of epithelial phenotypes.<\/jats:p>","DOI":"10.3390\/biom15081084","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T07:57:24Z","timestamp":1753689444000},"page":"1084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-Resolution Imaging and Interpretation of Three-Dimensional RPE Sheet Structure"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9144-3776","authenticated-orcid":false,"given":"Kevin J.","family":"Donaldson","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1366-5963","authenticated-orcid":false,"given":"Micah A.","family":"Chrenek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5875-492X","authenticated-orcid":false,"given":"Jeffrey H.","family":"Boatright","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Administration Center for Visual and Neurocognitive Rehabilitation, Decatur, GA 30033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-9897","authenticated-orcid":false,"given":"John M.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"ref_1","first-page":"898","article-title":"Analysis of RPE morphometry in human eyes","volume":"22","author":"Bhatia","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rickman, C.B., LaVail, M.M., Anderson, R.E., Grimm, C., Hollyfield, J., and Ash, J. (2016). RPE Cell and Sheet Properties in Normal and Diseased Eyes. Retinal Degenerative Diseases, Springer International Publishing.","DOI":"10.1007\/978-3-319-17121-0"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1038\/s41467-018-03856-y","article-title":"ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_5","first-page":"70","article-title":"Comparison of histologic findings in age-related macular degeneration with RPE flatmount images","volume":"25","author":"Zhang","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_6","first-page":"570","article-title":"Microscopic mammalian retinal pigment epithelium lesions induce widespread proliferation with differences in magnitude between center and periphery","volume":"16","author":"Ciurtin","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/BF02616175","article-title":"Culture of rat retinal pigment epithelium","volume":"13","author":"Edwards","year":"1977","journal-title":"In Vitro"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1006\/exer.1996.0020","article-title":"ARPE-19, a human retinal pigment epithelial cell line with differentiated properties","volume":"62","author":"Dunn","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1177\/1535370215587530","article-title":"Retinal pigment epithelial cell proliferation","volume":"240","author":"Stern","year":"2015","journal-title":"Exp. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108918","DOI":"10.1016\/j.exer.2021.108918","article-title":"Mechanisms of RPE senescence and potential role of \u03b1B crystallin peptide as a senolytic agent in experimental AMD","volume":"215","author":"Sreekumar","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.stemcr.2020.03.009","article-title":"Epigenomic and Transcriptomic Changes During Human RPE EMT in a Stem Cell Model of Epiretinal Membrane Pathogenesis and Prevention by Nicotinamide","volume":"14","author":"Boles","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_12","first-page":"1116","article-title":"Increased cell genesis in retinal pigment epithelium of perinatal vitiligo mutant mice","volume":"37","author":"Tang","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0012-1606(87)90152-7","article-title":"Growth and development of the mouse retinal pigment epithelium. I. Cell and tissue morphometrics and topography of mitotic activity","volume":"121","author":"Bodenstein","year":"1987","journal-title":"Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0012-1606(87)90153-9","article-title":"Growth and development of the mouse retinal pigment epithelium. II. Cell patterning in experimental chimaeras and mosaics","volume":"121","author":"Bodenstein","year":"1987","journal-title":"Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1167\/iovs.62.2.32","article-title":"Morphometric Analysis of Retinal Pigment Epithelial Cells From C57BL\/6J Mice During Aging","volume":"62","author":"Kim","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shelton, D.A., Gefke, I., Summers, V., Kim, Y.-K., Yu, H., Getz, Y., Ferdous, S., Donaldson, K., Liao, K., and Papania, J.T. (2024). Age-Related RPE changes in Wildtype C57BL\/6J Mice between 2 and 32 Months. BioRxiv, BioRxiv:2024.01.30.574142.","DOI":"10.1101\/2024.01.30.574142"},{"key":"ref_17","first-page":"103","article-title":"The retinal pigment epithelium","volume":"1998","author":"Marmor","year":"1998","journal-title":"Funct. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1167\/iovs.19-26949","article-title":"Quantifying Retinal Pigment Epithelium Dysmorphia and Loss of Histologic Autofluorescence in Age-Related Macular Degeneration","volume":"60","author":"Gambril","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2147\/OPTH.S2151","article-title":"Age and disease-related structural changes in the retinal pigment epithelium","volume":"2","author":"Bonilha","year":"2008","journal-title":"Clin. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.exer.2017.08.014","article-title":"Sorsby fundus dystrophy\u2014A review of pathology and disease mechanisms","volume":"165","author":"Christensen","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmg.40.9.641","article-title":"The genetics of inherited macular dystrophies","volume":"40","author":"Michaelides","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/cm.970130203","article-title":"Cytoskeletal organization of migrating retinal pigment epithelial cells during wound healing in organ culture","volume":"13","author":"Hergott","year":"1989","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1139\/o95-079","article-title":"Microfilament organization and wound repair in retinal pigment epithelium","volume":"73","author":"Kalnins","year":"1995","journal-title":"Biochem. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/acel.12447","article-title":"Retinal pigment epithelial cell multinucleation in the aging eye\u2014A mechanism to repair damage and maintain homoeostasis","volume":"15","author":"Chen","year":"2016","journal-title":"Aging Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Keeling, E., Chatelet, D.S., Tan, N.Y.T., Khan, F., Richards, R., Thisainathan, T., Goggin, P., Page, A., Tumbarello, D.A., and Lotery, A.J. (2020). 3D-Reconstructed Retinal Pigment Epithelial Cells Provide Insights into the Anatomy of the Outer Retina. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218408"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2014.01.004","article-title":"Oxidative stress induces mitochondrial dysfunction and a protective unfolded protein response in RPE cells","volume":"69","author":"Cano","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/978-1-4614-0631-0_81","article-title":"Analysis of the RPE sheet in the rd10 retinal degeneration model","volume":"723","author":"Chrenek","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.10.8.10","article-title":"Electrophysiologic and Morphologic Strain Differences in a Low-Dose NaIO3-Induced Retinal Pigment Epithelium Damage Model","volume":"10","author":"Zhang","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","article-title":"The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD","volume":"60","author":"Datta","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1080\/15548627.2022.2109286","article-title":"Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity","volume":"19","author":"Datta","year":"2023","journal-title":"Autophagy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109866","DOI":"10.1016\/j.celrep.2021.109866","article-title":"Proteomic and phosphoproteomic analyses identify liver-related signaling in retinal pigment epithelial cells during EMT","volume":"37","author":"Mertz","year":"2021","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sripathi, S.R., Hu, M.-W., Turaga, R.C., Mikeasky, R., Satyanarayana, G., Cheng, J., Duan, Y., Maruotti, J., Wahlin, K.J., and Berlinicke, C.A. (2023). IKK\u03b2 Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium. Cells, 12.","DOI":"10.3390\/cells12081155"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/iovs.62.4.1","article-title":"Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell-Derived RPE","volume":"62","author":"Sripathi","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100131","DOI":"10.1016\/j.mcpro.2021.100131","article-title":"Proteome Landscape of Epithelial-to-Mesenchymal Transition (EMT) of Retinal Pigment Epithelium Shares Commonalities With Malignancy-Associated EMT","volume":"20","author":"Sripathi","year":"2021","journal-title":"Mol. Cell. Proteom."},{"key":"ref_35","first-page":"1601","article-title":"\u201cGreen mice\u201d display limitations in enhanced green fluorescent protein expression in retina and optic nerve cells","volume":"29","author":"Caminos","year":"2014","journal-title":"Histol. Histopathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/eye.2010.149","article-title":"Retinal light toxicity","volume":"25","author":"Youssef","year":"2011","journal-title":"Eye"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1167\/iovs.66.2.49","article-title":"Accessible LED Lightbox for Light-induced Retinal Damage in Pigmented Mice","volume":"66","author":"Aliff","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","first-page":"624","article-title":"Alpha-catenin is a novel marker for identifying abnormal morphology following surgical damage of the RPE","volume":"58","author":"Donaldson","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","first-page":"4982","article-title":"Novel ex and in vivo methods for non-invasive longitudinal tracking of RPE dysmorphology following subretinal injections","volume":"59","author":"Donaldson","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/s41596-022-00689-4","article-title":"Subretinal injection in mice to study retinal physiology and disease","volume":"17","author":"Huang","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, X., Rai, U., Chung, J.-Y., and Esumi, N. (2021). Fine Tuning of an Oxidative Stress Model with Sodium Iodate Revealed Protective Effect of NF-\u03baB Inhibition and Sex-Specific Difference in Susceptibility of the Retinal Pigment Epithelium. Antioxidants, 11.","DOI":"10.3390\/antiox11010103"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/978-3-319-17121-0_59","article-title":"Exercise and Cyclic Light Preconditioning Protect Against Light-Induced Retinal Degeneration and Evoke Similar Gene Expression Patterns","volume":"854","author":"Chrenek","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1167\/iovs.07-1105","article-title":"Inducible expression of cre recombinase in the retinal pigmented epithelium","volume":"49","author":"Le","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_45","first-page":"40","article-title":"Methodologies for analysis of patterning in the mouse RPE sheet","volume":"21","author":"Boatright","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7274","DOI":"10.1167\/iovs.13-12450","article-title":"Functional Principal Component Analysis Reveals Discriminating Categories of Retinal Pigment Epithelial Morphology in Mice","volume":"54","author":"Jiang","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","first-page":"428","article-title":"An alternative means of retaining ocular structure and improving immunoreactivity for light microscopy studies","volume":"21","author":"Sun","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1093\/bioinformatics\/btt276","article-title":"TANGO: A generic tool for high-throughput 3D image analysis for studying nuclear organization","volume":"29","author":"Ollion","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rueden, C.T., Schindelin, J., Hiner, M.C., DeZonia, B.E., Walter, A.E., Arena, E.T., and Eliceiri, K.W. (2017). ImageJ2: ImageJ for the next generation of scientific image data. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1934-z"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/978-1-4614-3209-8_76","article-title":"Analysis of mouse RPE sheet morphology gives discriminatory categories","volume":"801","author":"Jiang","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1167\/iovs.19-26784","article-title":"Remodeling of the Basal Labyrinth of Retinal Pigment Epithelial Cells with Osmotic Challenge, Age, and Disease","volume":"60","author":"Hayes","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1167\/iovs.64.15.35","article-title":"Volumetric Reconstruction of a Human Retinal Pigment Epithelial Cell Reveals Specialized Membranes and Polarized Distribution of Organelles","volume":"64","author":"Lindell","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1167\/iovs.61.5.35","article-title":"Autofluorescent Granules of the Human Retinal Pigment Epithelium: Phenotypes, Intracellular Distribution, and Age-Related Topography","volume":"61","author":"Bermond","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1136\/bjophthalmol-2012-301547","article-title":"Autofluorescence imaging of human RPE cell granules using structured illumination microscopy","volume":"96","author":"Ach","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s00795-020-00277-z","article-title":"Quantitative volumetric analysis of the Golgi apparatus following X-ray irradiation by super-resolution 3D-SIM microscopy","volume":"54","author":"Oike","year":"2021","journal-title":"Med. Mol. Morphol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3","DOI":"10.21037\/aes-2021-01","article-title":"Characteristics of normal human retinal pigment epithelium cells with extremes of autofluorescence or intracellular granule count","volume":"6","author":"Bermond","year":"2021","journal-title":"Ann. Eye Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1136\/bjophthalmol-2012-302350","article-title":"High-resolution imaging of autofluorescent particles within drusen using structured illumination microscopy","volume":"97","author":"Rossberger","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1167\/iovs.18-24757","article-title":"Failure of Autophagy-Lysosomal Pathways in Rod Photoreceptors Causes the Early Retinal Degeneration Phenotype Observed in Cln6nclf Mice","volume":"59","author":"Grubman","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/s41467-019-08520-7","article-title":"Secreted metalloproteases ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth during ciliogenesis","volume":"10","author":"Nandadasa","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101882","DOI":"10.1016\/j.mito.2024.101882","article-title":"Machine learning-based 3D segmentation of mitochondria in polarized epithelial cells","volume":"76","author":"Hultgren","year":"2024","journal-title":"Mitochondrion"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1167\/iovs.63.1.23","article-title":"Autofluorescent Organelles Within the Retinal Pigment Epithelium in Human Donor Eyes with and Without Age-Related Macular Degeneration","volume":"63","author":"Bermond","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1167\/tvst.11.8.19","article-title":"Histologic Cell Shape Descriptors for the Retinal Pigment Epithelium in Age-Related Macular Degeneration: A Comparison to Unaffected Eyes","volume":"11","author":"Vaisband","year":"2022","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"15173","DOI":"10.1074\/jbc.M900322200","article-title":"Involvement of all-trans-retinal in acute light-induced retinopathy of mice","volume":"284","author":"Maeda","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e5215","DOI":"10.7717\/peerj.5215","article-title":"Ultrastructural alterations in the retinal pigment epithelium and photoreceptors of a Stargardt patient and three Stargardt mouse models: Indication for the central role of RPE melanin in oxidative stress","volume":"6","author":"Taubitz","year":"2018","journal-title":"PeerJ"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ng, E.S.Y., Kady, N., Hu, J., Dave, A., Jiang, Z., Pei, J., Gorin, M.B., Matynia, A., and Radu, R.A. (2022). Membrane Attack Complex Mediates Retinal Pigment Epithelium Cell Death in Stargardt Macular Degeneration. Cells, 11.","DOI":"10.3390\/cells11213462"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Volland, S., Esteve-Rudd, J., Hoo, J., Yee, C., and Williams, D.S. (2015). A comparison of some organizational characteristics of the mouse central retina and the human macula. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125631"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.semcdb.2016.05.010","article-title":"Epithelial cell extrusion: Pathways and pathologies","volume":"67","author":"Gudipaty","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Matsui, T. (2022). Calcium wave propagation during cell extrusion. Curr. Opin. Cell Biol., 76.","DOI":"10.1016\/j.ceb.2022.102083"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1084\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:16:44Z","timestamp":1760033804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/8\/1084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,26]]},"references-count":68,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["biom15081084"],"URL":"https:\/\/doi.org\/10.3390\/biom15081084","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.04.626881","asserted-by":"object"}]},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,26]]}}}