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Isabella Artner

Research team manager

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Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2 Diabetes

Author

  • 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

Summary, in English

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.

Department/s

  • Islet cell physiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Genomics, Diabetes and Endocrinology
  • History of Medicine
  • Internal Medicine - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Endocrine Cell Differentiation and Function
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2022

Language

English

Pages

858049-858049

Publication/Series

Frontiers in Neuroscience

Volume

16

Document type

Journal article

Publisher

Frontiers Media S. A.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Islet cell physiology
  • Genomics, Diabetes and Endocrinology
  • Internal Medicine - Epidemiology
  • Endocrine Cell Differentiation and Function

ISBN/ISSN/Other

  • ISSN: 1662-4548