{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:57:52Z","timestamp":1766138272407,"version":"3.41.2"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Glaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (A\u00df) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which A\u00df provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand A\u00df, have been shown to mediate neuronal loss <jats:italic>via<\/jats:italic> internalizing A\u00df within the neurons. In this study, we investigated whether the RAGE\u2013A\u00df axis plays a role in RGC loss in experimental glaucoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retinal ischemia was induced by an acute elevation of intraocular pressure in RAGE<jats:sup>\u2013\/\u2013<\/jats:sup> and wild-type (WT) control mice. In a subset of animals, oligomeric A\u00df was injected directly into the vitreous of both strains. RGC loss was assessed using histology and biochemical assays. Baseline and terminal positive scotopic threshold (pSTR) were also recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Retinal ischemia resulted in 1.9-fold higher RGC loss in WT mice compared to RAGE<jats:sup>\u2013\/\u2013<\/jats:sup> mice (36 \u00b1 3% <jats:italic>p<\/jats:italic> &amp;lt; 0.0001 vs. 19 \u00b1 2%, <jats:italic>p<\/jats:italic> = 0.004). Intravitreal injection of oligomeric A\u00df resulted in 2.3-fold greater RGC loss in WT mice compared to RAGE<jats:sup>\u2013\/\u2013<\/jats:sup> mice, 7-days post-injection (55 \u00b1 4% <jats:italic>p<\/jats:italic> = 0.008 vs. 24 \u00b1 2%, <jats:italic>p<\/jats:italic> = 0.02). We also found a significant decline in the positive scotopic threshold response (pSTR) amplitude of WT mice compared to RAGE<jats:sup>\u2013\/\u2013<\/jats:sup> (36 \u00b1 3% vs. 16 \u00b1 6%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>RAGE<jats:sup>\u2013\/\u2013<\/jats:sup> mice are protected against RGC loss following retinal ischemia. Intravitreal injection of oligomeric A\u00df accelerated RGC loss in WT mice but not RAGE<jats:sup>\u2013\/\u2013<\/jats:sup>. A co-localization of RAGE and A\u00df, suggests that RAGE\u2013A\u00df binding may contribute to RGC loss.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fncel.2023.1156084","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T05:34:40Z","timestamp":1681277680000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Nafiseh","family":"Seyed Hosseini Fin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Georgevsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria B.","family":"Sukkar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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