{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T23:12:54Z","timestamp":1780873974749,"version":"3.54.1"},"posted":{"date-parts":[[2024,9,19]]},"group-title":"Neuroscience","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <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 replicates these human POAG features accurately has been lacking. We report the development and characterization of a novel Cre-inducible mouse model expressing a DsRed-tagged Y437H mutant of human myocilin (\n                  <jats:italic>\n                    Tg.CreMYOC\n                    <jats:sup>Y<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>437<\/jats:sup>\n                  <jats:italic>\n                    <jats:sup>H<\/jats:sup>\n                  <\/jats:italic>\n                  ). A single intravitreal injection of HAd5-Cre induced selective MYOC expression in the TM, causing TM dysfunction, reducing outflow facility, and progressively elevating IOP in\n                  <jats:italic>\n                    Tg.CreMYOC\n                    <jats:sup>Y<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>437<\/jats:sup>\n                  <jats:italic>\n                    <jats:sup>H<\/jats:sup>\n                  <\/jats:italic>\n                  mice. Sustained IOP elevation resulted in significant retinal ganglion cell (RGC) loss and progressive axonal degeneration in Cre-induced\n                  <jats:italic>\n                    Tg.CreMYOC\n                    <jats:sup>Y<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>437<\/jats:sup>\n                  <jats:italic>\n                    <jats:sup>H<\/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>Y<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>437<\/jats:sup>\n                  <jats:italic>\n                    <jats:sup>H<\/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>Y<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>437<\/jats:sup>\n                  <jats:italic>\n                    <jats:sup>H<\/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":"10.1101\/2024.09.18.613712","type":"posted-content","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T07:55:17Z","timestamp":1726732517000},"source":"Crossref","is-referenced-by-count":2,"title":["Impaired axonal transport at the optic nerve head contributes to neurodegeneration in a novel Cre-inducible mouse model of myocilin glaucoma"],"prefix":"10.64898","author":[{"given":"Balasankara Reddy","family":"Kaipa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Kasetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogapriya","family":"Sundaresan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linya","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Yacoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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