{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:40:20Z","timestamp":1790109620348,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R21EY028273-01A1"],"award-info":[{"award-number":["R21EY028273-01A1"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["1RO1EY023557-01"],"award-info":[{"award-number":["1RO1EY023557-01"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY01583-26"],"award-info":[{"award-number":["P30EY01583-26"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted Funds"],"award-info":[{"award-number":["Unrestricted Funds"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"F.M. Kirby Foundation, and The Paul and Evanina Bell Mackall Foundation Trust","award":["Unrestricted Funds"],"award-info":[{"award-number":["Unrestricted Funds"]}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["EMR\/2016\/007068"],"award-info":[{"award-number":["EMR\/2016\/007068"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The genes in the 9p21 locus (CDKN2B-AS1 &amp; CDKN2B) are widely associated with Primary open-angle glaucoma (POAG). However, the functional importance of this locus in POAG pathogenesis is still unexplored. This study investigated the role of CDKN2BAS1-CDKN2B axis in POAG. We observed significant association of CDKN2B-AS1 SNP rs4977756 with POAG and its endophenotypic traits (vertical cup-disc ratio (p = 0.033) and central corneal thickness (p = 0.008)) by screening African American POAG cases (n = 1567) and controls (n = 1600). A luciferase reporter assay in Human embryonic kidney 293T (HEK293T) cells revealed that the region surrounding rs4977756 likely serves as a transcriptional repressor. siRNA-mediated knockdown of CDKN2B-AS1 in HEK293T cells and trabecular meshwork (TM) cells resulted in significantly increased expression of CDKN2B, which was also observed in human POAG ocular tissues. Pathway focused qRT-PCR gene expression analysis showed increased cellular senescence, TGF\u03b2 signaling and ECM deposition in TM cells after CDKN2B-AS1 suppression. In conclusion, we report that CDKN2B-AS1 may act as a regulator, and it could function by modulating the expression of CDKN2B. In addition, increase in CDKN2B levels due to CDKN2B-AS1 suppression may result in the senescence of trabecular meshwork cells leading to POAG pathogenesis.<\/jats:p>","DOI":"10.3390\/cells9091934","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T09:21:51Z","timestamp":1598001711000},"page":"1934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Molecular Genetics and Functional Analysis Implicate CDKN2BAS1-CDKN2B Involvement in POAG Pathogenesis"],"prefix":"10.3390","volume":"9","author":[{"given":"Sonika","family":"Rathi","sequence":"first","affiliation":[{"name":"Scheie Eye Institute, Department of Ophthalmology, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Danford","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, Department of Ophthalmology, Philadelphia, PA 19104, USA"},{"name":"Casey Eye Institute, Oregon Health &amp; Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harini V.","family":"Gudiseva","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, Department of Ophthalmology, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana","family":"Verkuil","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, Department of Ophthalmology, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4266-4150","authenticated-orcid":false,"given":"Maxwell","family":"Pistilli","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, Department of Ophthalmology, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushma","family":"Vishwakarma","sequence":"additional","affiliation":[{"name":"Prof Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, Telangana 500034, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3660-5039","authenticated-orcid":false,"given":"Inderjeet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Prof Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, Telangana 500034, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarjani Vivek","family":"Dave","sequence":"additional","affiliation":[{"name":"Ophthalmic Plastic Surgery Service, Prof Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, Telangana 500034, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan M.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, Department of Ophthalmology, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3439-3490","authenticated-orcid":false,"given":"Venkata R. M.","family":"Chavali","sequence":"additional","affiliation":[{"name":"Scheie Eye Institute, Department of Ophthalmology, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"ref_1","unstructured":"Mahabadi, N., Foris, L.A., and Tripathy, K. (2020). Open Angle Glaucoma. 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