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We have shown that caspase-2 caused the death of retinal ganglion cells (RGC) after blunt ocular trauma. Here, we investigated if caspase-2 also mediates RGC apoptosis in a mouse model of air blast induced indirect traumatic optic neuropathy (b-ITON). C57BL\/6 mice were exposed to repeated blasts of overpressure air (3\u2009\u00d7\u20092\u2009\u00d7\u200915 psi) and intravitreal injections of siRNA against caspase-2 (siCASP2) or against a control enhanced green fluorescent protein (siEGFP) at either 5 h after the first 2\u2009\u00d7\u200915 psi (\u201cpost-blast\u201d) or 48\u00a0h before the first blast exposure (\u201cpre-blast\u201d) and repeated every 7\u00a0days. RGC counts were unaffected by the b-ITON or intravitreal injections, despite increased degenerating ON axons, even in siCASP2 \u201cpost-blast\u201d injection groups. Degenerating ON axons remained at sham levels after b-ITON and intravitreal siCASP2 \u201cpre-blast\u201d injections, but with less degenerating axons in siCASP2 compared to siEGFP-treated eyes. Intravitreal injections \u201cpost-blast\u201d caused greater vitreous inflammation, potentiated by siCASP2, with less in \u201cpre-blast\u201d injected eyes, which was abrogated by siCASP2. We conclude that intravitreal injection timing after ocular trauma induced variable retinal and ON pathology, undermining our candidate neuroprotective therapy, siCASP2.<\/jats:p>","DOI":"10.1038\/s41598-021-96107-y","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T10:30:05Z","timestamp":1629369005000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma"],"prefix":"10.1038","volume":"11","author":[{"given":"Chloe N.","family":"Thomas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Bernardo-Col\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Courtie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth","family":"Essex","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonia S.","family":"Rex","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Blanch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zubair","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"96107_CR1","doi-asserted-by":"publisher","first-page":"17032","DOI":"10.1038\/cddiscovery.2017.32","volume":"3","author":"CN Thomas","year":"2017","unstructured":"Thomas, C. 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