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Volume 27
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10.3390/ijms27010048
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone

by
Patricia 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
1
Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
2
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
3
Ophthalmology Research Group, Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2026, 27(1), 48; https://doi.org/10.3390/ijms27010048 (registering DOI)
Submission received: 24 October 2025 / Revised: 16 December 2025 / Accepted: 17 December 2025 / Published: 20 December 2025
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
Versions Notes

Abstract

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 primary open-angle glaucoma; dexamethasone-induced experimental model; dipeptidyl peptidase 4 inhibitors; sitagliptin; eye drops

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MDPI and ACS Style

Bogdanov, P.; Duarri, A.; Sabater, D.; Canz, M.J.; Isla-Magrané, H.; Ramos, H.; Deàs-Just, A.; Simó, R.; Hernández, C. Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone. Int. J. Mol. Sci. 2026, 27, 48. https://doi.org/10.3390/ijms27010048

AMA Style

Bogdanov P, Duarri A, Sabater D, Canz MJ, Isla-Magrané H, Ramos H, Deàs-Just A, Simó R, Hernández C. Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone. International Journal of Molecular Sciences. 2026; 27(1):48. https://doi.org/10.3390/ijms27010048

Chicago/Turabian Style

Bogdanov, Patricia, Anna Duarri, David Sabater, María José Canz, Helena Isla-Magrané, Hugo Ramos, Anna Deàs-Just, Rafael Simó, and Cristina Hernández. 2026. "Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone" International Journal of Molecular Sciences 27, no. 1: 48. https://doi.org/10.3390/ijms27010048

APA Style

Bogdanov, P., Duarri, A., Sabater, D., Canz, M. J., Isla-Magrané, H., Ramos, H., Deàs-Just, A., Simó, R., & Hernández, C. (2026). Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone. International Journal of Molecular Sciences, 27(1), 48. https://doi.org/10.3390/ijms27010048

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