Neuromodulation Induced by Sitagliptin: A New Strategy for Treating Diabetic Retinopathy
| العنوان: | Neuromodulation Induced by Sitagliptin: A New Strategy for Treating Diabetic Retinopathy |
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| المؤلفون: | Cristina Hernández, David Sabater, Jordi Huerta, Patricia Bogdanov, Hugo Ramos, Marta Valeri, Rafael Simó |
| المساهمون: | Institut Català de la Salut, [Ramos H, Bogdanov P, Hernández C, Simó R] Unitat de Recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain. [Sabater D, Huerta J] Unitat de Recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Valeri M] Unitat d'Alta Tecnologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Biomedicines Biomedicines; Volume 9; Issue 12; Pages: 1772 Scientia Biomedicines, Vol 9, Iss 1772, p 1772 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | enfermedades del sistema endocrino::diabetes mellitus::complicaciones de la diabetes::angiopatías diabéticas::retinopatía diabética [ENFERMEDADES], Synapsin I, Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Angiopathies::Diabetic Retinopathy [DISEASES], QH301-705.5, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors::Dipeptidyl-Peptidase IV Inhibitors [CHEMICALS AND DRUGS], diabetic retinopathy, retinal neurodegeneration, dipeptidyl peptidase 4 inhibitors, sitagliptin, presynaptic proteins, db/db mouse model, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Medicine (miscellaneous), Pharmacology, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Peptidases - Inhibidors, General Biochemistry, Genetics and Molecular Biology, Article, Downregulation and upregulation, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteasas::inhibidores de la dipeptidil-peptidasa IV [COMPUESTOS QUÍMICOS Y DROGAS], Medicine, Other subheadings::/therapeutic use [Other subheadings], Biology (General), biology, VAMP2, Otros calificadores::/uso terapéutico [Otros calificadores], STX1A, business.industry, SNAP25, Retinopatia diabètica - Tractament, Membrane protein, Sitagliptin, Synaptophysin, biology.protein, business, medicine.drug |
| الوصف: | Presynaptic proteins; Retinal neurodegeneration; Sitagliptin Proteínas presinápticas; Neurodegeneración retiniana; Sitagliptina Proteïnes presinàptiques; Neurodegeneració retiniana; Sitagliptina Diabetic retinopathy (DR) involves progressive neurovascular degeneration of the retina. Reduction in synaptic protein expression has been observed in retinas from several diabetic animal models and human retinas. We previously reported that the topical administration (eye drops) of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, prevented retinal neurodegeneration induced by diabetes in db/db mice. The aim of the present study is to examine whether the modulation of presynaptic proteins is a mechanism involved in the neuroprotective effect of sitagliptin. For this purpose, 12 db/db mice, aged 12 weeks, received a topical administration of sitagliptin (5 μL; concentration: 10 mg/mL) twice per day for 2 weeks, while other 12 db/db mice were treated with vehicle (5 μL). Twelve non-diabetic mice (db/+) were used as a control group. Protein levels were assessed by western blot and immunohistochemistry (IHC), and mRNA levels were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Our results revealed a downregulation (protein and mRNA levels) of several presynaptic proteins such as synapsin I (Syn1), synaptophysin (Syp), synaptotagmin (Syt1), syntaxin 1A (Stx1a), vesicle-associated membrane protein 2 (Vamp2), and synaptosomal-associated protein of 25 kDa (Snap25) in diabetic mice treated with vehicle in comparison with non-diabetic mice. These proteins are involved in vesicle biogenesis, mobilization and docking, membrane fusion and recycling, and synaptic neurotransmission. Sitagliptin was able to significantly prevent the downregulation of all these proteins. We conclude that sitagliptin exerts beneficial effects in the retinas of db/db mice by preventing the downregulation of crucial presynaptic proteins. These neuroprotective effects open a new avenue for treating DR as well other retinal diseases in which neurodegeneration/synaptic abnormalities play a relevant role. This research was funded by grants from the Ministerio de Economía y Competitividad (PID2019-104225RB-I00) and the Instituto de Salud Carlos III (DTS18/0163, PI19/01215, and ICI20/00129). The study funder was not involved in the design of the study. |
| وصف الملف: | application/pdf |
| تدمد: | 2227-9059 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b076def10a6de6c3603dcc632979dfddTest https://pubmed.ncbi.nlm.nih.gov/34944588Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b076def10a6de6c3603dcc632979dfdd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22279059 |
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