{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:10:24Z","timestamp":1787803824971,"version":"build-2784847793"},"posted":{"date-parts":[[2025,12,23]]},"group-title":"Neuroscience","reference-count":98,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R01EY035088"],"award-info":[{"award-number":["R01EY035088"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Career-starter Research Grant"],"award-info":[{"award-number":["Career-starter Research Grant"]}],"id":[{"id":"https:\/\/ror.org\/03mq5pg65","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"crossref","award":["National Glaucoma Research Award"],"award-info":[{"award-number":["National Glaucoma Research Award"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Retinal ganglion cell (RGC) degeneration in optic neuropathies is often preceded by neuroinflammatory changes, yet the earliest\n                  <jats:italic>in vivo<\/jats:italic>\n                  indicators of this process remain poorly defined. Here, we identified vitreous hyperreflective foci (VHRFs) by visible-light optical coherence tomography (vis-OCT) as an early inflammatory signature of RGC injury. Longitudinal vis-OCT imaging after optic nerve crush (ONC) revealed that VHRFs emerged as early as 6 hours post-injury and peaked before the significant RGC loss. Confocal analysis showed that these VHRFs corresponded to activated amoeboid microglia undergoing vertical migration from the outer to inner retina and horizontal movement toward the optic nerve head area. Similar amoeboid microglia were also observed in the anterior segment, suggesting a global ocular inflammatory response to the ONC injury. RNAscope\n                  <jats:italic>in situ<\/jats:italic>\n                  hybridization further demonstrated elevated\n                  <jats:italic>IL-1\u03b2<\/jats:italic>\n                  expression in vitreous amoeboid microglia. Moreover, pharmacological blockade of IL-1 signaling with an IL-1 receptor antagonist significantly reduced VHRFs, suppressed microglial migration, and delayed RGC loss. Taken together, our findings identify VHRFs as a previously unrecognized early danger signal for RGC degeneration and highlight IL-1\u2013mediated inflammation as a tractable early therapeutic target for preventing RGC degeneration and vision loss.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Overview<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"694725v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.20.694725","type":"posted-content","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T22:35:11Z","timestamp":1766529311000},"source":"Crossref","is-referenced-by-count":1,"title":["Vitreous Inflammation as an Early Indicator of Retinal Ganglion Cell Loss 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