{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:57:13Z","timestamp":1793383033639,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Cell motility\u2014the dynamic process encompassing migration, adhesion modulation, cytoskeletal remodeling, and extracellular matrix (ECM) interactions\u2014is fundamental to ocular homeostasis. In glaucoma, disrupted motility of trabecular meshwork (TM) and Schlemm\u2019s canal (SC) cells contributes to impaired aqueous humor outflow and elevated intraocular pressure (IOP), while reactive motility of optic nerve head (ONH) glial cells promotes fibrosis and neurodegeneration. Mechanistically, TM\/SC motility is regulated by Rho GTPase and ROCK signaling, focal adhesion dynamics, and ECM interactions, while glial cells respond to mechanical stress and cytokines such as TGF-\u03b22. Cytoskeletal alterations, ECM stiffening, and endothelial\u2013mesenchymal transition (EndMT) contribute to glaucomatous damage by reducing normal cell motility and tissue remodeling capacity. Aberrant motility at the ONH, including heterogeneous astrocytic reactivity, leads to lamina cribrosa remodeling and retinal ganglion cell degeneration. Therapeutically, ROCK inhibitors improve TM\/SC motility and outflow, suppress EndMT, and may confer neuroprotection. Stem cell-based strategies and modulation of TGF-\u03b22 or mechanotransduction pathways represent emerging approaches to restore physiological motility and regenerative potential. Despite promising advances, challenges remain in ensuring targeted, durable, and safe modulation of cellular dynamics. Understanding and therapeutically harnessing cell motility offers a unifying framework to address both pressure-dependent and neurodegenerative mechanisms in glaucoma.<\/jats:p>","DOI":"10.3390\/medicina61122219","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:36:53Z","timestamp":1765895813000},"page":"2219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cell Motility Dynamics in Glaucoma: Mechanisms, Pathogenic Roles, and Therapeutic Targeting"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-2585","authenticated-orcid":false,"given":"Dario","family":"Rusciano","sequence":"first","affiliation":[{"name":"Fidia Pharmaceuticals, Ophthalmology Research, Catania University, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-876X","authenticated-orcid":false,"given":"Alessandro","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Neurovisual Science Technology (NEST), 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3808-8944","authenticated-orcid":false,"given":"Jos\u00e9 Fernando","family":"Maya-Vetencourt","sequence":"additional","affiliation":[{"name":"Department of Biology, Physiology Institute, University of Pisa, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175882","DOI":"10.1016\/j.ejphar.2023.175882","article-title":"Glaucoma: Novel antifibrotic therapeutics for the trabecular meshwork","volume":"954","author":"Qin","year":"2023","journal-title":"Eur. 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