{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:19:32Z","timestamp":1785845972939,"version":"3.56.0"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["EY034333,EY026177"],"award-info":[{"award-number":["EY034333,EY026177"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["EY034238"],"award-info":[{"award-number":["EY034238"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"crossref","award":["unrestricted grant to to the Gavin Herbert Eye Institute at the University of California,Irvine."],"award-info":[{"award-number":["unrestricted grant to to the Gavin Herbert Eye Institute at the University of California,Irvine."]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:p>\n                    Elevation of intraocular pressure (IOP) due to trabecular meshwork (TM) dysfunction, leading to neurodegeneration, is the pathological hallmark of primary open-angle glaucoma (POAG). Impaired axonal transport is an early and critical feature of glaucomatous neurodegeneration. However, a robust mouse model that accurately replicates these human POAG features has been lacking. We report the development and characterization of a new Cre-inducible mouse model expressing a DsRed-tagged Y437H mutant of human myocilin (\n                    <jats:italic>\n                      Tg.CreMYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    ). A single intravitreal injection of HAd5-Cre induced selective MYOC expression in the TM, causing TM dysfunction, reducing the outflow facility, and progressively elevating IOP in\n                    <jats:italic>\n                      Tg.CreMYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Sustained IOP elevation resulted in significant loss of retinal ganglion cells (RGCs) and progressive axonal degeneration in Cre-induced\n                    <jats:italic>\n                      Tg.CreMYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Notably, impaired anterograde axonal transport was observed at the optic nerve head before RGC degeneration, independent of age, indicating that impaired axonal transport contributes to RGC degeneration in\n                    <jats:italic>\n                      Tg.CreMYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    mice. In contrast, axonal transport remained intact in ocular hypertensive mice injected with microbeads, despite significant RGC loss. Our findings indicate that Cre-inducible\n                    <jats:italic>\n                      Tg.CreMYOC\n                      <jats:sup>Y437H<\/jats:sup>\n                    <\/jats:italic>\n                    mice replicate all glaucoma phenotypes, providing an ideal model for studying early events of TM dysfunction and neuronal loss in POAG.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.188710","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T12:00:56Z","timestamp":1737460856000},"source":"Crossref","is-referenced-by-count":11,"title":["Impaired axonal transport contributes to neurodegeneration in a Cre-inducible mouse model of myocilin-associated glaucoma"],"prefix":"10.1172","volume":"10","author":[{"given":"Balasankara Reddy","family":"Kaipa","sequence":"first","affiliation":[{"name":"Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, and"},{"name":"Department of Physiology and Biophysics, University of California Irvine School of Medicine, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7874-3988","authenticated-orcid":true,"given":"Ramesh","family":"Kasetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogapriya","family":"Sundaresan","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, and"},{"name":"Department of Physiology and Biophysics, University of California Irvine School of Medicine, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linya","family":"Li","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, and"},{"name":"Department of Physiology and Biophysics, University of California Irvine School of Medicine, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Cameron","family":"Millar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Cho","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, and"},{"name":"Department of Physiology and Biophysics, University of California Irvine School of Medicine, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-4225","authenticated-orcid":true,"given":"Dorota","family":"Skowronska-Krawczyk","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology, and"},{"name":"Department of Physiology and Biophysics, University of 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