Photoreceptor glucose metabolism determines normal retinal vascular growth

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The neural cells and factors determining normal vascular growth are not well defined even though vision-threatening neovessel growth, a major cause of blindness in retinopathy of prematurity (ROP) (and diabetic retinopathy), is driven by delayed normal vascular growth. We here examined whether hyperglycemia and low adiponectin (APN) levels delayed normal retinal vascularization, driven primarily by dysregulated photoreceptor metabolism. In premature infants, low APN levels correlated with hyperglycemia and delayed retinal vascular formation. Experimentally in a neonatal mouse model of postnatal hyperglycemia modeling early ROP, hyperglycemia caused photoreceptor dysfunction and delayed neurovascular maturation associated with changes in the APN pathway; recombinant mouse APN or APN receptor agonist AdipoRon treatment normalized vascular growth. APN deficiency decreased retinal mitochondrial metabolic enzyme levels particularly in photoreceptors, suppressed retinal vascular development, and decreased photoreceptor platelet-derived growth factor (Pdgfb). APN pathway activation reversed these effects. Blockade of mitochondrial respiration abolished AdipoRon-induced Pdgfb increase in photoreceptors. Photoreceptor knockdown of Pdgfb delayed retinal vascular formation. Stimulation of the APN pathway might prevent hyperglycemia-associated retinal abnormalities and suppress phase I ROP in premature infants.

Detaljer

Författare
  • Zhongjie Fu
  • Chatarina A. Löfqvist
  • Raffael Liegl
  • Zhongxiao Wang
  • Ye Sun
  • Yan Gong
  • Chi Hsiu Liu
  • Steven S. Meng
  • Samuel B. Burnim
  • Ivana Arellano
  • My T. Chouinard
  • Rubi Duran
  • Alexander Poblete
  • Steve S. Cho
  • James D. Akula
  • Michael Kinter
  • Saswata Talukdar
  • Ann Hellström
  • Lois Eh Smith
Enheter & grupper
Externa organisationer
  • Oklahoma Medical Research Foundation
  • Boston Children's Hospital
  • Harvard University
  • Göteborgs universitet
  • Merck Research Laboratories
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
  • Oftalmologi

Nyckelord

Originalspråkengelska
Sidor (från-till)76-90
TidskriftEMBO Molecular Medicine
Volym10
Utgivningsnummer1
Tidigt onlinedatum2017 nov 27
StatusPublished - 2018 jan
PublikationskategoriForskning
Peer review utfördJa