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Uveitis in mice is induced by intravitreal lipopolysaccharide, followed by bulk RNA sequencing, PCR quantification of cytosolic mitochondrial DNA, and timed assessment of cGAS–STING activation by western blotting. Cgas knockout mice, along with fundus imaging, fluorescein angiography, microstructural and histopathological scoring, and retinal leukocytosis assays, show that cGAS loss markedly suppresses vitreous inflammation, vascular leakage, leukocyte adhesion, macrophage infiltration and activation, and microglial activation, indicating cGAS as a potential therapeutic target for uveitis.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cgas-knockout-inhibited-endotoxin-induced-uveitis-in-mice/418130/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cgas-knockout-inhibited-endotoxin-induced-uveitis-in-mice/418130.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How is endotoxin-induced uveitis induced in the mouse model in this study?","Question",{"text":113,"@type":114},"Endotoxin-induced uveitis is provoked by intravitreal administration of lipopolysaccharide (LPS).","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What methods are used to evaluate activation of the cGAS–STING pathway?",{"text":118,"@type":114},"The study uses transcriptome analysis via bulk RNA sequencing, PCR quantification of cytosolic mitochondrial DNA levels in the retina, and western blotting at specified times after intravitreal LPS injection.",{"name":120,"@type":111,"acceptedAnswer":121},"What overall effect does cGAS knockout have on ocular inflammation?",{"text":122,"@type":114},"Cgas knockout significantly inhibits endotoxin-induced intraocular inflammation, including reduced vitreous inflammation, reduced retinal vascular leakage, decreased leukocyte adhesion, inhibited leukocyte infiltration and macrophage activation, and inhibited microglial activation.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},418130,1790742405,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Genes & Diseases (2026) 13, 101786  \nAvailable online [at](at www.sciencedirect.com)[ www.sciencedirect.com](at www.sciencedirect.com)  \nScienceDirect  \njournal [homepage:](homepage: www . keaipublishing. com/en/journals/genes-diseases)[ www . keaipublishing. com/en/journals/genes-diseases](homepage: www . keaipublishing. com/en/journals/genes-diseases)  \nFULL LENGTH ARTICLE  \ncGAS knockout inhibited endotoxin-induced uveitis in mice  \nYue Guo a,b,c,d,e,f, Ruiping Gu a,b,c,d,f, Jiaojiao Wei Chunhui Jiang a,b,c,d,**  \na,b,c,d,*,  \na Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China b Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China  \nc Eye Institute, Eye and ENT Hospital of Fudan University, Shanghai 200031, China  \nd Key Laboratory of Myopia of State Health Ministry, Shanghai 200031, China e Department of Ophthalmology, Peking University People’s Hospital, Beijing 100044, China  \nReceived 22 September 2024; received in revised form 28 May 2025; accepted 31 May 2025 Available online 29 July 2025  \nKEYWORDS  \ncGAS;  \nEIU;  \nLipopolysaccharide; Retina;  \nSTING  \nAbstract Our research focused on the impact of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)—stimulator of interferon genes (STING) pathway on retinal inflammation and employed an endotoxin-induced uveitis (EIU) model. EIU was provoked in mice through the intravitreal administration of lipopolysaccharide. Transcriptome analysis was performed via bulk RNA sequencing. Cytosolic mitochondrial DNA levels in theretina were quantified via PCR. Western blotting was used to assess the activation of cGAS‒ STING signaling at specified times after intravitreal lipopolysaccharide injection. To understand the influence of the cGAS‒STING pathway on inflammatory retinal disorders, Cgas knockout mice were developed. Fundus imaging and fluorescein angiography were conducted to observe vitreous inflammation. Microstructural analysis of the eyes was performed, and histopathological scoring was performed. Retinal leukocytosis assays were used to evaluate retinal inflammation. Analysis of these differentially expressed mRNAs revealed activation of the cGAS‒STING signaling pathway, which was confirmed by western blotting analysis of these proteins. Using Cgas knockout mice, we observed significant inhibition of endotoxininduced intraocular inflammation, including reduced vitreous inflammation, reduced retinal vascular leakage, decreased leukocyte adhesion, inhibited infiltration and activation of macrophages in the retina, and inhibited microglial activation. These findings suggest that cGAS might be a potential novel therapeutic target for uveitis.  \n* Corresponding author. Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China.  \n** Corresponding author. Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China.  \nE-mail [addresses:](addresses: weijiaojiao0121@126.com)[ weijiaojiao0121@126.com](addresses: weijiaojiao0121@126.com) (J. Wei), [chhjiang70@163.com](chhjiang70@163.com) (C. Jiang).  \nPeer review under the responsibility of Chongqing Medical University.  \nf These authors contributed equally to this work.  \n[https://doi.org/10.1016/j.gendis.2025.101786](https://doi.org/10.1016/j.gendis.2025.101786)  \n2352-3042/© 2025 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. , Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)).  \n© 2025 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. , Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/](http://creativecommons.org/)[ ](http://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/) ) .  \nIntroduction  \nCyclic guanosine mon","cbCaie9aa219CPsg","https://ap.wps.com/l/cbCaie9aa219CPsg","pdf",11005804,14,"English","# Introduction\n## cGAS–STING pathway as a DNA sensor and inflammatory mediator\n## Evidence of cGAS–STING involvement across diseases and ocular inflammation","[{\"question\":\"How is endotoxin-induced uveitis induced in the mouse model in this study?\",\"answer\":\"Endotoxin-induced uveitis is provoked by intravitreal administration of lipopolysaccharide (LPS).\"},{\"question\":\"What methods are used to evaluate activation of the cGAS–STING pathway?\",\"answer\":\"The study uses transcriptome analysis via bulk RNA sequencing, PCR quantification of cytosolic mitochondrial DNA levels in the retina, and western blotting at specified times after intravitreal LPS injection.\"},{\"question\":\"What overall effect does cGAS knockout have on ocular inflammation?\",\"answer\":\"Cgas knockout significantly inhibits endotoxin-induced intraocular inflammation, including reduced vitreous inflammation, reduced retinal vascular leakage, decreased leukocyte adhesion, inhibited leukocyte infiltration and macrophage activation, and inhibited microglial activation.\"}]","cGAS knockout inhibited endotoxin-induced uveitis in mice | PDF",1790612101,35]