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Interleukin-1\u03b2 (IL-1\u03b2) is an important inflammatory factor involved in the pathology of retinal IR injury, but the mechanism by which IL-1\u03b2 is regulated in such injury remains unclear. Caspase-11 non-canonical inflammasomes can regulate the synthesis and secretion of IL-1\u03b2, but its role in retinal IR injury has not been elucidated. This study aimed to evaluate the role of caspase-11 non-canonical inflammasomes in retinal IR injury.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Retinal IR injury was induced in C57BL\/6J mice by increasing the intraocular pressure to 110 mmHg for 60 min. The post-injury changes in retinal morphology and function and in IL-1\u03b2 expression were compared between caspase-11 gene knockout (caspase-11<jats:sup>\u2212\/\u2212<\/jats:sup>) mice and wild-type (WT) mice. Morphological and functional changes were evaluated using hematoxylin\u2013eosin staining and retinal whole mount staining and using electroretinography (ERG), respectively. IL-1\u03b2 expression in the retina was measured using enzyme-linked immunosorbent assay (ELISA). The levels of caspase-11-related protein were measured using western blot analysis. The location of caspase-11 in the retina was determined via immunofluorescence staining. Mouse type I astrocytes C8-D1A cells were used to validate the effects of caspase-11 simulation via hypoxia in vitro. Small-interfering RNA targeting caspase-11 was constructed. Cell viability was evaluated using the MTT assay. IL-1\u03b2 expression in supernatant and cell lysate was measured using ELISA. The levels of caspase-11-related protein were measured using western blot analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Retinal ganglion cell death and retinal edema were more ameliorated, and the ERG b-wave amplitude was better after retinal IR injury in caspase-11<jats:sup>\u2212\/\u2212<\/jats:sup> mice than in WT mice. Further, caspase-11<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed lower protein expressions of IL-1\u03b2, cleaved caspase-1, and gasdermin D (GSDMD) in the retina after retinal IR injury. Caspase-11 protein was expressed in retinal glial cells, and caspase-11 knockdown played a protective role against hypoxia in C8-D1A cells. The expression levels of IL-1\u03b2, cleaved caspase-1, and GSDMD were inhibited after hypoxia in the si-caspase-11 constructed cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Retinal IR injury activates caspase-11 non-canonical inflammasomes in glial cells of the retina. This results in increased protein levels of GSDMD and IL-1\u03b2 and leads to damage in the inner layer of the retina.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10020-024-00938-0","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T10:02:04Z","timestamp":1727431324000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of caspase-11 non-canonical inflammasomes in retinal ischemia\/reperfusion injury"],"prefix":"10.1186","volume":"30","author":[{"given":"Yong","family":"Wan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialei","family":"Pu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Pei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8838-8577","authenticated-orcid":false,"given":"Yun","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"938_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-021-02237-5","volume":"18","author":"SF Abcouwer","year":"2021","unstructured":"Abcouwer SF, Shanmugam S, Muthusamy A. 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