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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,5,12]]},"abstract":"<jats:p>\n                    Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From \u223c24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque (\n                    <jats:italic>Macaca fascicularis<\/jats:italic>\n                    ), rhesus macaque (\n                    <jats:italic>Macaca mulatta<\/jats:italic>\n                    ), pig (\n                    <jats:italic>Sus scrofa<\/jats:italic>\n                    ), and mouse (\n                    <jats:italic>Mus musculus<\/jats:italic>\n                    ). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2001250117","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T20:29:47Z","timestamp":1588019387000},"page":"10339-10349","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":240,"title":["Cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-9894","authenticated-orcid":false,"given":"Tav\u00e9","family":"van Zyl","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear, Boston, MA 02114;"},{"name":"Center for Brain Science, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Yan","sequence":"additional","affiliation":[{"name":"Center for Brain Science, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexi","family":"McAdams","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear, Boston, MA 02114;"},{"name":"Center for Brain Science, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Rong","family":"Peng","sequence":"additional","affiliation":[{"name":"Center for Brain Science, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Shekhar","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142;"},{"name":"Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Regev","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142;"},{"name":"Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;"},{"name":"Klarman Cell Observatory, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejan","family":"Juric","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School and Massachusetts General Hospital Cancer Center, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8926-8836","authenticated-orcid":false,"given":"Joshua R.","family":"Sanes","sequence":"additional","affiliation":[{"name":"Center for Brain Science, Harvard University, Cambridge, MA 02138;"},{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley H. 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