a1b7fd11e0ce73947bee8631e9e0ae07 ijms-27-00048.pdf 0fa9a5219cbb577d843a611015171cde2fb92a55 ijms-27-00048.pdf fc41f557e1c690d42ac381ca3308b80042b0fc3eedb7de712bb3a20105e32dc6 ijms-27-00048.pdf Title: Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone Subject: Glaucoma 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 diabetes-induced 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 < 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 < 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. Keywords: primary open-angle glaucoma; dexamethasone-induced experimental model; dipeptidyl peptidase 4 inhibitors; sitagliptin; eye drops Author: Patricia Bogdanov, Anna Duarri, David Sabater, María José Canz, Helena Isla-Magrané, Hugo Ramos, Anna Deàs-Just, Rafael Simó and Cristina Hernández Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Tue Dec 23 08:55:48 2025 CET ModDate: Tue Dec 23 09:34:23 2025 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4341918 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WNWTFR+VnURWPalladioL-Bold Type 1 Custom yes yes yes 159 0 ZWMQST+URWPalladioL-Ital Type 1 Custom yes yes yes 160 0 SSXPJJ+VnURWPalladioL Type 1 Custom yes yes yes 161 0 DGVIKG+URWPalladioL-Bold Type 1 Custom yes yes yes 162 0 ZNLNNS+URWPalladioL-Roma Type 1 Custom yes yes yes 163 0 VYVZGZ+CMSY10 Type 1 Builtin yes yes yes 239 0 BBSDEQ+EURM10 Type 1 Builtin yes yes yes 249 0 JGNHPG+PalatinoLinotype TrueType WinAnsi yes yes no 233 0 GEWEQC+PazoMath-Italic Type 1 Builtin yes yes yes 281 0 JGNHPG+PalatinoLinotype TrueType WinAnsi yes yes no 275 0 JGNHPI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 306 0 JGNHPG+PalatinoLinotype TrueType WinAnsi yes yes no 307 0 JGNHPE+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 308 0 JGNHPG+PalatinoLinotype TrueType WinAnsi yes yes no 339 0 JGNHPG+PalatinoLinotype TrueType WinAnsi yes yes no 316 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-02-27 04:51:21 CET RepresentationInformation: ijms-27-00048.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-02-26 14:28:19 CET Size: 4341918 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 603 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Results Children: Item: Title: IOP Assessments Item: Title: Ocular Assessment Item: Title: Sitagliptin Prevented RGCs Loss Item: Title: Sitagliptin Prevented Oligodendrocytes Loss in the ONH Item: Title: Sitagliptin Reduced the Astroglial Activation in the ONH and the Retina Item: Title: Sitagliptin Reduced the Microglial Activation in the ONH Item: Title: Sitagliptin Inhibits the Overexpression of Galectin-3 (MAC-2) and Gamma-Synuclein (-Synuclein) in the ONH Item: Title: Sitagliptin Decreased the Overexpression of Pro-Inflammatory Cytokines in the ONH Item: Title: Discussion Item: Title: Materials and Methods Children: Item: Title: Animals Item: Title: Dexamethasone Periocular Administration, Multimodal Imaging, and Topical Treatment with Sitagliptin Item: Title: Intraocular Pressure (IOP) Measurement Item: Title: Immunofluorescence of the Neuroretina, ONH Sections and Retinal Wholemounts Item: Title: Quantification of RGCs in Retinal Tissues Item: Title: Quantification of Fluorescent Immunostainings in Optic Nerve Head (ONH) Item: Title: Macroglial Activation Item: Title: Microglial Molecular Signature Item: Title: Galectin 3 (MAC-2) and Gamma-Synuclein (-Synuclein) Item: Title: Oligodendrocyte Transcription Factor 2 (Oligo-2) Item: Title: RNA Isolation and qRT-PCR Item: Title: Statistical Analysis Item: Title: Conclusions Item: Title: References Info: Title: Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone Author: Patricia Bogdanov, Anna Duarri, David Sabater, María José Canz, Helena Isla-Magrané, Hugo Ramos, Anna Deàs-Just, Rafael Simó and Cristina Hernández Subject: Glaucoma 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 diabetes-induced 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 < 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 < 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. 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