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Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis

View ORCID ProfileTavé van Zyl, Wenjun Yan, Alexi McAdams, Yi-Rong Peng, Karthik Shekhar, Aviv Regev, Dejan Juric, View ORCID ProfileJoshua R. Sanes
doi: https://doi.org/10.1101/2020.02.04.933911
Tavé van Zyl
1Department of Ophthalmology, Harvard Medical School, Boston, MA 02114
2Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
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  • ORCID record for Tavé van Zyl
  • For correspondence: sanesj@mcb.harvard.edu tave_vanzyl@meei.harvard.edu
Wenjun Yan
2Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
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Alexi McAdams
1Department of Ophthalmology, Harvard Medical School, Boston, MA 02114
2Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
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Yi-Rong Peng
2Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
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Karthik Shekhar
3Howard Hughes Medical Institute, Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140; and Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142
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Aviv Regev
3Howard Hughes Medical Institute, Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140; and Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142
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Dejan Juric
4Massachusetts General Hospital, Boston, MA, 02114
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Joshua R. Sanes
2Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138
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  • ORCID record for Joshua R. Sanes
  • For correspondence: sanesj@mcb.harvard.edu tave_vanzyl@meei.harvard.edu
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ABSTRACT

Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells that carry information from the eye to the brain; 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 (scRNA-seq). From ∼24,000 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 (Macaca fascicularis), rhesus macaque (Macaca mulatta), pig (Sus scrofa) and mouse (Mus musculus). 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.

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Posted February 04, 2020.
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Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis
Tavé van Zyl, Wenjun Yan, Alexi McAdams, Yi-Rong Peng, Karthik Shekhar, Aviv Regev, Dejan Juric, Joshua R. Sanes
bioRxiv 2020.02.04.933911; doi: https://doi.org/10.1101/2020.02.04.933911
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Cell Atlas of Aqueous Humor Outflow Pathways in Eyes of Humans and Four Model Species Provides Insights into Glaucoma Pathogenesis
Tavé van Zyl, Wenjun Yan, Alexi McAdams, Yi-Rong Peng, Karthik Shekhar, Aviv Regev, Dejan Juric, Joshua R. Sanes
bioRxiv 2020.02.04.933911; doi: https://doi.org/10.1101/2020.02.04.933911

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