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Past studies investigating these diabetes-induced retinal vascular abnormalities have focused primarily on the role of molecular or biochemical cues. Here we show that retinal vascular inflammation and degeneration in diabetes are also mechanically regulated by the increase in retinal vascular stiffness caused by overexpression of the collagen\u2013cross-linking enzyme lysyl oxidase (LOX). Treatment of diabetic mice with LOX inhibitor \u03b2-aminopropionitrile (BAPN) prevented the increase in retinal capillary stiffness, vascular intracellular adhesion molecule-1 overexpression, and leukostasis. Consistent with these anti-inflammatory effects, BAPN treatment of diabetic mice blocked the upregulation of proapoptotic caspase-3 in retinal vessels, which concomitantly reduced retinal capillary degeneration, pericyte ghost formation, and the diabetes-induced loss of contrast sensitivity in these mice. Finally, our in\u00a0vitro studies indicate that retinal capillary stiffening is sufficient to increase the adhesiveness and neutrophil elastase-induced death of retinal endothelial cells. By uncovering a link between LOX-dependent capillary stiffening and the development of retinal vascular and functional defects in diabetes, these findings offer a new insight into DR pathogenesis that has important translational potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db23-0584","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T03:17:51Z","timestamp":1700536671000},"page":"280-291","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":14,"title":["Mechanical Regulation of Retinal Vascular Inflammation and Degeneration in 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Western Reserve University, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Kiser","sequence":"additional","affiliation":[{"name":"4Department of Ophthalmology, Center for Translational Vision Research, University of California, Irvine, Irvine, CA"},{"name":"5Gavin Herbert Eye Institute, University of California, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"7Department of Bioengineering, University of California, Riverside, Riverside, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"2Doheny Eye Institute, Pasadena, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Kern","sequence":"additional","affiliation":[{"name":"4Department of Ophthalmology, Center for Translational Vision Research, University of 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