{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:45:51Z","timestamp":1768585551949,"version":"3.49.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              The ANGPT (angiopoietin)-TEK (tyrosine kinase, endothelial) vascular signaling pathway plays a key role in the formation of Schlemm canal, and loss-of-function mutations in the\n              <jats:italic toggle=\"yes\">TEK<\/jats:italic>\n              or\n              <jats:italic toggle=\"yes\">ANGPT1<\/jats:italic>\n              gene are associated with primary congenital glaucoma in children. In genome-wide association studies, an association was identified between protection from primary open-angle glaucoma and the single-nucleotide polymorphism rs76020419 (G&gt;T), located within a predicted\n              <jats:italic toggle=\"yes\">miR-145<\/jats:italic>\n              \u2013binding site in the 3\u2032 untranslated region of\n              <jats:italic toggle=\"yes\">ANGPT2<\/jats:italic>\n              . To date, the functional impact of this variant in the anterior chamber of the eye remains largely unexplored.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>MT (mutant) mice harboring an orthologous rs76020419 minor allele (T) were generated using CRISPR\/Cas9 (clustered regularly interspaced short palindromic repeats\/clustered regularly interspaced short palindromic repeat\u2013associated 9). Plasma and tissue samples, including eyes, were collected, and ANGPT2 expression was quantified using ELISA. Anterior segments from eyes were collected from WT (wild-type) and MT mice, and Schlemm canal area was quantified.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              In the MT group, higher ANGPT2 concentrations were observed in the plasma, lungs, kidneys, and eyes (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0212,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001,\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0815, and\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0215, respectively). Additionally, the Schlemm canal was larger in MT mice compared with WT mice (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.0430).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>The rs76020419 minor allele (T) is associated with increased levels of ANGPT2 and a larger Schlemm canal in mice. These findings suggest a potential protective mechanism in glaucoma.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.124.321555","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T09:13:12Z","timestamp":1724922792000},"page":"2207-2212","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Glaucoma-Protective Human Single-Nucleotide Polymorphism in the\n            <i>Angpt2<\/i>\n            Locus Increased ANGPT2 Expression and Schlemm Canal Area in Mice\u2014Brief Report"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4613-7048","authenticated-orcid":true,"given":"Naoki","family":"Kiyota","sequence":"first","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."},{"name":"Division of Nephrology and Hypertension (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8891-2300","authenticated-orcid":true,"given":"Tuncer","family":"Onay","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."},{"name":"Division of Nephrology and Hypertension (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0530-0153","authenticated-orcid":true,"given":"Phoebe","family":"Leeaw","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."},{"name":"Division of Nephrology and Hypertension (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3066-652X","authenticated-orcid":true,"given":"Pan","family":"Liu","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."},{"name":"Division of Nephrology and Hypertension (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilip K.","family":"Deb","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."},{"name":"Division of Nephrology and Hypertension (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-5866","authenticated-orcid":true,"given":"Benjamin R.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."},{"name":"Division of Nephrology and Hypertension (N.K., T.O., P. Leeaw, P. Liu, D.K.D., B.R.T., S.E.Q.), Northwestern University Feinberg School of Medicine, Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-5845","authenticated-orcid":true,"given":"Ayellet V.","family":"Segr\u00e8","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ocular Genomics Institute, Massachusetts Eye and Ear, Boston (A.V.S., J.L.W.)."},{"name":"Department of Ophthalmology, Harvard Medical School, Boston, MA (A.V.S., J.L.W.)."},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA (A.V.S., J.L.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-3278","authenticated-orcid":true,"given":"Janey L.","family":"Wiggs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ocular Genomics Institute, Massachusetts Eye and Ear, Boston (A.V.S., J.L.W.)."},{"name":"Department of Ophthalmology, Harvard Medical School, Boston, MA (A.V.S., J.L.W.)."},{"name":"Broad Institute of Harvard and MIT, Cambridge, MA (A.V.S., J.L.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-5727","authenticated-orcid":true,"given":"Susan E.","family":"Quaggin","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute (N.K., T.O., P. 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