Sistema de Salut de Catalunya
Institut Català de la Salut
[Ramos H] Grup de Recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain. [Augustine J, Karan BM, Stitt AW, Curtis TM] Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry & Biomedical Science, Queen’s University Belfast, Belfast, Northern Ireland, UK. [Hernández C, Simó R] Grup de Recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-01-16T12:30:34Z
2025-01-16T12:30:34Z
2024-11-30
Diabetes; Diabetic retinopathy; Sitagliptin
Diabetis; Retinopatia diabètica; Sitagliptina
Diabetes; Retinopatía diabética; Sitagliptina
Impaired function of the retinal neurovascular unit (NVU) is an early event in diabetic retinopathy (DR). It has been previously shown that topical delivery of the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin can protect against diabetes-mediated dysfunction of the retinal NVU in the db/db mouse. The aim of the present study was to examine whether sitagliptin could prevent the DR-like lesions within the NVU of the new non-diabetic model of DR, the Trpv2 knockout rat (Trpv2+/−). For that purpose, at 3 months of age, Trpv2+/− rats were topically treated twice daily for two weeks with sitagliptin or PBS-vehicle eyedrops. Trpv2+/+ rats treated with vehicle served as the control group. Body weight and glycemia were monitored. Optical coherence tomography recordings, fundus images and retinal samples were obtained to evaluate sitagliptin effects. The results revealed that sitagliptin eye drops had no effect on body weight or glycemia. Vehicle-treated Trpv2+/− rats exhibited retinal thinning and larger diameters of major retinal blood vessels, upregulation of inflammatory factors and oxidative markers, glial activation and formation of acellular capillaries. However, topical administration of sitagliptin significantly prevented all these abnormalities. In conclusion, sitagliptin eye drops exert a protective effect against DR-like lesions in Trpv2+/− rats. Our results suggest that sitagliptin eye drops carry significant potential to treat not only early-stages of DR but also other diseases with impairment of the NVU unrelated to diabetes.
We are grateful to EAsDEC skills award program, Belfast Association for the Blind, MICIN (PID2022-138544OB-I00), ISCIII (ICI20/00129), Biotechnology and Biological Sciences Research Council (BB/I026359/1) and Diabetes UK (18/0005791) for funding this work.
Artículo
Versión publicada
Inglés
Retinopatia diabètica - Tractament; Enzims proteolítics - Inhibidors - Ús terapèutic; Solucions (Farmàcia); Rates (Animals de laboratori); Tomografia de coherència òptica; DISEASES::Eye Diseases::Retinal Diseases::Diabetic Retinopathy; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Rats; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors; Other subheadings::Other subheadings::/therapeutic use; CHEMICALS AND DRUGS::Pharmaceutical Preparations::Solutions::Pharmaceutical Solutions::Ophthalmic Solutions; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Optical Imaging::Tomography, Optical::Tomography, Optical Coherence; ENFERMEDADES::oftalmopatías::enfermedades de la retina::retinopatía diabética; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratas; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteasas; Otros calificadores::Otros calificadores::/uso terapéutico; COMPUESTOS QUÍMICOS Y DROGAS::preparados farmacéuticos::soluciones::soluciones farmacéuticas::soluciones oftálmicas; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::imágenes ópticas::tomografía óptica::tomografía de coherencia óptica
BMC
Journal of Neuroinflammation;21
https://doi.org/10.1186/s12974-024-03283-5
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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