Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes
| العنوان: | Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes |
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| المؤلفون: | Olena Fedotkina, Ruchi Jain, Rashmi B. Prasad, Andrea Luk, Marta García-Ramírez, Türküler Özgümüs, Liubov Cherviakova, Nadiya Khalimon, Tetiana Svietleisha, Tetiana Buldenko, Victor Kravchenko, Deepak Jain, Allan Vaag, Juliana Chan, Mykola D. Khalangot, Cristina Hernández, Peter M. Nilsson, Rafael Simo, Isabella Artner, Valeriya Lyssenko |
| المساهمون: | Institut Català de la Salut, [Fedotkina O, Özgümüs T] Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway. [Jain R, Prasad RB] Department of Clinical Sciences, Lund University Diabetes Center, Skane University Hospital, Malmö, Sweden. [Luk A] Prince of Wales Hospital, Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China. [García-Ramírez M, Simo R] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBERDEM, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia Frontiers in Neuroscience |
| بيانات النشر: | Frontiers Media, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | enfermedades del sistema endocrino::diabetes mellitus::complicaciones de la diabetes::angiopatías diabéticas::retinopatía diabética [ENFERMEDADES], enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo de la glucosa::diabetes mellitus::diabetes mellitus tipo II [ENFERMEDADES], Sistema nerviós - Malalties, Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Angiopathies::Diabetic Retinopathy [DISEASES], afecciones patológicas, signos y síntomas::procesos patológicos::degeneración nerviosa [ENFERMEDADES], General Neuroscience, Diabetis no-insulinodependent - Complicacions, Retinopatia diabètica, Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [DISEASES], Pathological Conditions, Signs and Symptoms::Pathologic Processes::Nerve Degeneration [DISEASES] |
| الوصف: | Diabetic retinopathy; Famine; Neuronal function Retinopatía diabética; Hambruna; Función neuronal Retinopatia diabètica; Fam; Funció neuronal Persons with type 2 diabetes born in the regions of famine exposures have disproportionally elevated risk of vision-threatening proliferative diabetic retinopathy (PDR) in adulthood. However, the underlying mechanisms are not known. In the present study, we aimed to investigate the plausible molecular factors underlying progression to PDR. To study the association of genetic variants with PDR under the intrauterine famine exposure, we analyzed single nucleotide polymorphisms (SNPs) that were previously reported to be associated with type 2 diabetes, glucose, and pharmacogenetics. Analyses were performed in the population from northern Ukraine with a history of exposure to the Great Ukrainian Holodomor famine [the Diagnostic Optimization and Treatment of Diabetes and its Complications in the Chernihiv Region (DOLCE study), n = 3,583]. A validation of the top genetic findings was performed in the Hong Kong diabetes registry (HKDR, n = 730) with a history of famine as a consequence of the Japanese invasion during WWII. In DOLCE, the genetic risk for PDR was elevated for the variants in ADRA2A, PCSK9, and CYP2C19*2 loci, but reduced at PROX1 locus. The association of ADRA2A loci with the risk of advanced diabetic retinopathy in famine-exposed group was further replicated in HKDR. The exposure of embryonic retinal cells to starvation for glucose, mimicking the perinatal exposure to famine, resulted in sustained increased expression of Adra2a and Pcsk9, but decreased Prox1. The exposure to starvation exhibited a lasting inhibitory effects on neurite outgrowth, as determined by neurite length. In conclusion, a consistent genetic findings on the famine-linked risk of ADRA2A with PDR indicate that the nerves may likely to be responsible for communicating the effects of perinatal exposure to famine on the elevated risk of advanced stages of diabetic retinopathy in adults. These results suggest the possibility of utilizing neuroprotective drugs for the prevention and treatment of PDR. This work was supported by the Swedish Research Council (Dnr2015-03574 and Dnr349-2006-237), Strategic Research Area Exodiab (Dnr2009-1039), the Novonordisk Foundation (NNF12OC1016467), Swedish Foundation for Strategic Research (DnrIRC15-0067), the Steno Diabetes Center Copenhagen, Bergen Research Foundation and Trond Mohn Foundation (BFS811294), and the University of Bergen. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a7c3bd5c4a796a19d5b332f23628c99Test https://hdl.handle.net/11351/8096Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a7c3bd5c4a796a19d5b332f23628c99 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |