Photoreceptor glucose metabolism determines normal retinal vascular growth

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


title = "Photoreceptor glucose metabolism determines normal retinal vascular growth",
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.",
keywords = "Adiponectin, Hyperglycemia, Metabolism, Photoreceptor, Retinopathy of prematurity",
author = "Zhongjie Fu and L{\"o}fqvist, {Chatarina A.} and Raffael Liegl and Zhongxiao Wang and Ye Sun and Yan Gong and Liu, {Chi Hsiu} and Meng, {Steven S.} and Burnim, {Samuel B.} and Ivana Arellano and Chouinard, {My T.} and Rubi Duran and Alexander Poblete and Cho, {Steve S.} and Akula, {James D.} and Michael Kinter and David Ley and Pupp, {Ingrid Hansen} and Saswata Talukdar and Ann Hellstr{\"o}m and Smith, {Lois Eh}",
year = "2018",
month = "1",
doi = "10.15252/emmm.201707966",
language = "English",
volume = "10",
pages = "76--90",
journal = "EMBO Molecular Medicine",
issn = "1757-4684",
publisher = "Federation of European Neuroscience Societies and Blackwell Publishing Ltd",
number = "1",