{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:48:01Z","timestamp":1789069681109,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Youth Development Project of Air Force Military Medical University","award":["No. 21QNPY072"],"award-info":[{"award-number":["No. 21QNPY072"]}]},{"name":"Youth Development Project of Air Force Military Medical University","award":["2023-JC-ZD-48"],"award-info":[{"award-number":["2023-JC-ZD-48"]}]},{"name":"Key Project of Shaanxi Provincial Natural Science Basic Research Progra","award":["No. 21QNPY072"],"award-info":[{"award-number":["No. 21QNPY072"]}]},{"name":"Key Project of Shaanxi Provincial Natural Science Basic Research Progra","award":["2023-JC-ZD-48"],"award-info":[{"award-number":["2023-JC-ZD-48"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Retinal ischemia, after cerebral ischemia, is an easily overlooked pathophysiological problem in which inflammation is considered to play an important role. Pyroptosis is a kind of cell death pattern accompanied by inflammation. Homer scaffold protein 1 (Homer1) has anti-inflammation properties and protects against ischemic injury. However, little is known about pyroptosis following middle cerebral artery occlusion (MCAO)-induced retinal ischemia and the regulatory mechanisms involved by Homer1 for the development of pyroptosis. In the present study, retinal ischemic injury was induced in mice by permanent MCAO in vivo, and retinal ganglion cells (RGCs) were subjected to Oxygen and Glucose Deprivation (OGD) to establish an in vitro model. It was shown that TXNIP\/NLRP3-mediated pyroptosis was located predominantly in RGCs, which gradually increased after retinal ischemia and peaked at 24 h after retinal ischemia. Interestingly, the RGCs pyroptosis occurred not only in the cell body but also in the axon. Notably, the occurrence of pyroptosis coincided with the change of Homer1 expression in the retina after retinal ischemia and Homer1 also co-localized with RGCs. It was demonstrated that overexpression of Homer1 not only alleviated RGCs pyroptosis and inhibited the release of pro-inflammatory factors but also led to the increase in phosphorylation of AMPK, inhibition of ER stress, and preservation of visual function after retinal ischemia. In conclusion, it was suggested that Homer1 may protect against MCAO-induced retinal ischemia and RGCs pyroptosis by inhibiting endoplasmic reticulum stress-associated TXNIP\/NLRP3 inflammasome activation after MCAO-induced retinal ischemia.<\/jats:p>","DOI":"10.3390\/ijms242316811","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T07:56:10Z","timestamp":1701071770000},"page":"16811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Homer1 Protects against Retinal Ganglion Cell Pyroptosis by Inhibiting Endoplasmic Reticulum Stress-Associated TXNIP\/NLRP3 Inflammasome Activation after Middle Cerebral Artery Occlusion-Induced Retinal Ischemia"],"prefix":"10.3390","volume":"24","author":[{"given":"Weihao","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuquan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1038\/s41418-018-0058-y","article-title":"RGMa mediates reactive astrogliosis and glial scar formation through TGF\u03b21\/Smad2\/3 signaling after stroke","volume":"25","author":"Zhang","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1177\/0271678X17731956","article-title":"Maternal high-fat diet programs cerebrovascular remodeling in adult rat offspring","volume":"38","author":"Lin","year":"2018","journal-title":"J. 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