Open AccessPhotoreceptor glucose metabolism determines normal retinal vascular growth
Author(s) -
Fu Zhongjie,
Löfqvist Chatarina A,
Liegl Raffael,
Wang Zhongxiao,
Sun Ye,
Gong Yan,
Liu ChiHsiu,
Meng Steven S,
Burnim Samuel B,
Arellano Ivana,
Chouinard My T,
Duran Rubi,
Poblete Alexander,
Cho Steve S,
Akula James D,
Kinter Michael,
Ley David,
Pupp Ingrid Hansen,
Talukdar Saswata,
Hellström Ann,
Smith Lois EH
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201707966
Subject(s) - retinal , carbohydrate metabolism , metabolism , retina , biology , endocrinology , medicine , biochemistry , neuroscience
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.