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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorFedotkina, Olena
dc.contributor.authorJain, Ruchi
dc.contributor.authorPrasad, Rashmi B.
dc.contributor.authorLuk, Andrea
dc.contributor.authorGarcía Ramírez, Marta
dc.contributor.authorOzgumus, Turkuler
dc.contributor.authorSimó Canonge, Rafael
dc.date.accessioned2022-09-09T08:24:03Z
dc.date.available2022-09-09T08:24:03Z
dc.date.issued2022-05-05
dc.identifier.citationFedotkina O, Jain R, Prasad RB, Luk A, García-Ramírez M, Özgümüs T, et al. Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes. Front Neurosci. 2022 May 5;16:858049.
dc.identifier.issn1662-453X
dc.identifier.urihttp://hdl.handle.net/11351/8096
dc.descriptionDiabetic retinopathy; Famine; Neuronal function
dc.description.abstractPersons 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.
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.ispartofseriesFrontiers in Neuroscience;16
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectDiabetis no-insulinodependent - Complicacions
dc.subjectRetinopatia diabètica
dc.subjectSistema nerviós - Malalties
dc.subject.meshDiabetic Retinopathy
dc.subject.meshNerve Degeneration
dc.subject.meshDiabetes Mellitus, Type 2
dc.titleNeuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3389/fnins.2022.858049
dc.subject.decsretinopatía diabética
dc.subject.decsdegeneración nerviosa
dc.subject.decsdiabetes mellitus tipo II
dc.relation.publishversionhttps://doi.org/10.3389/fnins.2022.858049
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[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
dc.identifier.pmid35600617
dc.identifier.wos000798022600001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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