δ Opioid receptor agonism preserves the retinal pigmented epithelial cell tight junctions and ameliorates the retinopathy in experimental diabetes
| العنوان: | δ Opioid receptor agonism preserves the retinal pigmented epithelial cell tight junctions and ameliorates the retinopathy in experimental diabetes |
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| المؤلفون: | De Faria, J.M.L., Duarte, D.A., Simó, R., García-Ramirez, M., Dátilo, M.N., Pasqualetto, F.C., De Faria, J.B.L., Universitat Autònoma de Barcelona |
| المساهمون: | [Lopes de Faria JM, Duarte DA, Dátilo MN, Pasqualetto FC] Renal Pathophysiology Laboratory, Investigation on Diabetes Complications, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil. [Simó R, García-Ramirez M] 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 (ISCIII), Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Scientia |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Blood Glucose, Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Angiopathies::Diabetic Retinopathy [DISEASES], Retinal pigmented epithelial, Retinal Pigment Epithelium, Occludin, Catechin, Mice, chemistry.chemical_compound, 0302 clinical medicine, Diabetic retinopathy, Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Opioid::Receptors, Opioid, delta [CHEMICALS AND DRUGS], Receptors, Opioid, delta, Claudin-1, Electric Impedance, RNA, Small Interfering, Retina - Vasos sanguinis, Fluorescent Antibody Technique, Indirect, aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores acoplados a proteínas G::receptores opioides::receptores opiodes delta [COMPUESTOS QUÍMICOS Y DROGAS], Tight junction, Diabetes, Middle Aged, Immunohistochemistry, medicine.anatomical_structure, Female, Retinopathy, enfermedades del sistema endocrino::diabetes mellitus::complicaciones de la diabetes::angiopatías diabéticas::retinopatía diabética [ENFERMEDADES], medicine.medical_specialty, Cardiovascular System::Blood-Retinal Barrier [ANATOMY], Blotting, Western, Blood–retinal barrier, Real-Time Polymerase Chain Reaction, Diabetes Mellitus, Experimental, Tight Junctions, 03 medical and health sciences, Neurotransmissors - Receptors, Downregulation and upregulation, Internal medicine, Glial Fibrillary Acidic Protein, medicine, Animals, Humans, Nerve Growth Factors, Eye Proteins, Serpins, Aged, Retina, D opioid receptor, Diabetic Retinopathy, Retinal, medicine.disease, sistema cardiovascular::barrera hematorretinal [ANATOMÍA], eye diseases, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Retinopatia diabètica, Zonula Occludens-1 Protein, sense organs, 030217 neurology & neurosurgery |
| الوصف: | Supported by the European Foundation for Study of Diabetes and Sanofi in the Collaborative Clinical Diabetes Research between European and Non-European Countries Programme. DAD received a scholarship from FAPESP (2015/23258-9). PURPOSE. Outer blood retinal barrier breakdown is a neglected feature of diabetic retinopathy (DR). We demonstrated that the agonism of the δ opioid receptor (DOR) by epicatechin preserves the tight junction proteins in ARPE-19 cells under diabetic conditions. Presently, we aimed to evaluate the possible role of the DOR on the maintenance of tight junction of RPE layer and on the early markers of experimental DR. METHODS. DR markers and external retinal tight junction proteins were evaluated in CL57B diabetic mice submitted to intravitreous injection of short hairpin RNA (shRNA)-DOR (108 transducing units [TU]/mL) treated or not with DOR agonist (0.05 g/animal/d of epicatechin in drinking water) for 16 weeks. The presence of DOR in human retina from postmortem eyes from diabetic and nondiabetic donors were also performed. RESULTS. DOR is present in RPE layer and in neuro retina. The treatment with DOR agonist prevented the upregulation of the early markers of retinopathy (glial fibrillary acidic protein, VEGF) and the downregulation of pigment epithelium-derived factor, occludin, claudin-1, and zonula occludens-1 tight junction expressions. The silencing of DOR in retina of diabetic mice partially abolished the protective effects of epicatechin. In human retina specimens, DOR is present throughout the retina, similarly in nondiabetic and diabetic donors. CONCLUSIONS. This set of experiments strongly indicates that the DOR agonism preserves RPE tight junctions and reduces the early markers of retinopathy in model of diabetes. These novel findings designate DOR as a potential therapeutic tool to treat DR with preservation of the RPE tight junction proteins. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d54a731b8ab704c54dcf1259d7a8dfcfTest https://ddd.uab.cat/record/223802Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d54a731b8ab704c54dcf1259d7a8dfcf |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |