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This study tested whether sitagliptin eye drops could prevent dexamethasone-induced glaucoma in mice. DEX caused substantial RGC and optic nerve axon loss, which sitagliptin prevented without altering IOP (p \u003C 0.001). Sitagliptin also reduced DEX-driven activation of macroglia and microglia and prevented oligodendrocyte loss, suppressing galectin-3 and gamma-synuclein overexpression in the optic nerve head, supporting therapeutic potential.",{"@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/topical-administration-of-sitagliptin-prevents-retinal-neurodegeneration-in-a-model-of-glaucoma-induced-by-dexamethasone/462115/",{"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/topical-administration-of-sitagliptin-prevents-retinal-neurodegeneration-in-a-model-of-glaucoma-induced-by-dexamethasone/462115.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What was the main goal of the study?","Question",{"text":113,"@type":114},"To determine whether sitagliptin eye drops could prevent corticosteroid-induced glaucoma in a dexamethasone-induced mouse model.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was glaucoma induced in the mice?",{"text":118,"@type":114},"Glaucoma was induced by periocular injection of dexamethasone (DEX) once weekly for five weeks.",{"name":120,"@type":111,"acceptedAnswer":121},"Did sitagliptin affect intraocular pressure (IOP)?",{"text":122,"@type":114},"No. Sitagliptin prevented neurodegeneration without affecting IOP.","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},462115,1791034609,{"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},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Article  \nTopical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone  \nPatricia Bogdanov 1,2, *,†, Anna Duarri 3,†, David Sabater 1,2, María José Canz 1, Helena Isla-Magrané 3, Hugo Ramos 1,2, Anna Deàs-Just 1, Rafael Simó 1,2, * and Cristina Hernández 1,2  \nAcademic Editors: Livio Vitiello and Deokho Lee  \nReceived: 24 October 2025  \nRevised: 16 December 2025  \nAccepted: 17 December 2025  \nPublished: 20 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain; [david.sabater@vhir.org](david.sabater@vhir.org) (D.S.); [maria.canz@vhir.org](maria.canz@vhir.org) (M.J.C.); [hugo.ramos@vhir.org](hugo.ramos@vhir.org) (H.R.); [anna.deas@vhir.org](anna.deas@vhir.org) (A.D.-J.); [cristina.hernandez@vhir.org](cristina.hernandez@vhir.org) (C.H.)  \n2 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain  \n3 Ophthalmology Research Group, Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain; [anna.duarri@vhir.org](anna.duarri@vhir.org) (A.D.); [helena.isla@gmail.com](helena.isla@gmail.com) (H.I.-M.)  \n* [Correspondence: patricia.bogdanov@vhir.org](Correspondence: patricia.bogdanov@vhir.org) (P.B.); [rafael.simo@vhir.org](rafael.simo@vhir.org) (R.S.)† These authors contributed equally to this work.  \nAbstract  \nGlaucoma is a neurodegenerative disease characterized by progressive degeneration of optic nerve axons and loss of retinal ganglion cells (RGCs) . Although elevated intraocular pressure (IOP) is a major risk factor, many patients develop glaucoma with normal IOP, highlighting the need for neuroprotective therapies. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, has shown beneficial effects in diabetes-induced retinal neurodegeneration. This study aimed to evaluate whether sitagliptin eye drops, previously effective in diabetesinduced retinal neurodegeneration, could prevent corticosteroid-induced glaucoma. Glaucoma was induced in mice by periocular injection of dexamethasone (DEX) once weekly for five weeks. Sitagliptin or vehicle eye drops were administered from day 14 to 35 . Untreated mice served as controls. DEX treatment caused significant loss of RGC bodies and optic nerve axons compared to controls, which was prevented by sitagliptin eye drops (p \u003C 0.001), without affecting IOP. Sitagliptin also inhibited DEX-induced activation of macroglia and microglia and prevented oligodendrocyte loss. Furthermore, it suppressed overexpression of galectin-3 and gamma-synuclein in the optic nerve head (ONH) (p \u003C 0.001), key mediators of inflammation and apoptosis. Sitagliptin eye drops exert a potent neuroprotective effect against corticosteroid-induced glaucoma, supporting their potential as a novel therapeutic strategy for glaucoma.  \nKeywords: primary open-angle glaucoma; dexamethasone-induced experimental model; dipeptidyl peptidase 4 inhibitors; sitagliptin; eye drops  \n1. Introduction  \nGlaucoma, a group of diseases characterized by progressive optic neuropathy, is oneof the leading causes of severe visual impairment and blindness worldwide. The global prevalence of glaucoma for the population aged 40–80 years is 3.54%, and it is estimated that it affects around 111.8 million people worldwide by 2040 [1] . This neurodegenerative disease causes the progressive degeneration of optic nerve axons and the retrograde death of retinal ganglion cells (RGCs), leading to visual impairment that may progress to blindness  \nin 10% of cases. It should be highlighted that more than half are unaware that they are affected, as the disease often remains asymptomatic until it is se","cbCais457vEvH5Yv","https://ap.wps.com/l/cbCais457vEvH5Yv","pdf",4341918,17,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What was the main goal of the study?\",\"answer\":\"To determine whether sitagliptin eye drops could prevent corticosteroid-induced glaucoma in a dexamethasone-induced mouse model.\"},{\"question\":\"How was glaucoma induced in the mice?\",\"answer\":\"Glaucoma was induced by periocular injection of dexamethasone (DEX) once weekly for five weeks.\"},{\"question\":\"Did sitagliptin affect intraocular pressure (IOP)?\",\"answer\":\"No. Sitagliptin prevented neurodegeneration without affecting IOP.\"}]","Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone | PDF",1790763301,43]