{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:51:28Z","timestamp":1790056288309,"version":"4.0.1"},"reference-count":70,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natiional Eye Institute","award":["EY026177,EY028616,EY030366"],"award-info":[{"award-number":["EY026177,EY028616,EY030366"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,8]]},"abstract":"<jats:p>\n                    Elevation of intraocular pressure (IOP) due to trabecular meshwork (TM) damage is associated with primary open-angle glaucoma (POAG). Myocilin mutations resulting in elevated IOP are the most common genetic causes of POAG. We have previously shown that mutant myocilin accumulates in the ER and induces chronic ER stress, leading to TM damage and IOP elevation. However, it is not understood how chronic ER stress leads to TM dysfunction and loss. Here, we report that mutant myocilin activated autophagy but was functionally impaired in cultured human TM cells and in a mouse model of myocilin-associated POAG (\n                    <jats:italic>\n                      Tg-MYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    ). Genetic and pharmacological inhibition of autophagy worsened mutant myocilin accumulation and exacerbated IOP elevation in\n                    <jats:italic>\n                      Tg-MYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Remarkably, impaired autophagy was associated with chronic ER stress\u2013induced transcriptional factor CHOP. Deletion of CHOP corrected impaired autophagy, enhanced recognition and degradation of mutant myocilin by autophagy, and reduced glaucoma in\n                    <jats:italic>\n                      Tg-MYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Stimulating autophagic flux via tat-beclin 1 peptide or torin 2 promoted autophagic degradation of mutant myocilin and reduced elevated IOP in\n                    <jats:italic>\n                      Tg-MYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Our study provides an alternate treatment strategy for myocilin-associated POAG by correcting impaired autophagy in the TM.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.143359","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T12:18:58Z","timestamp":1612441138000},"source":"Crossref","is-referenced-by-count":54,"title":["Autophagy stimulation reduces ocular hypertension in a murine glaucoma model via autophagic degradation of mutant myocilin"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7874-3988","authenticated-orcid":true,"given":"Ramesh B.","family":"Kasetti","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience and the North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, 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