Photoreceptor glucose metabolism determines normal retinal vascular growth
Male
0301 basic medicine
570
Medicine (General)
Vascular Biology & Angiogenesis
610
QH426-470
Retinal Neovascularization
Cell Line
03 medical and health sciences
R5-920
Genetics
retinopathy of prematurity
Animals
Humans
Retinopathy of Prematurity
Research Articles
adiponectin
Infant, Newborn
Retinal Vessels
photoreceptor
3. Good health
Mice, Inbred C57BL
Glucose
Hyperglycemia
Female
hyperglycemia
Adiponectin
metabolism
Infant, Premature
Metabolism, Inborn Errors
Neuroscience
Photoreceptor Cells, Vertebrate
DOI:
10.15252/emmm.201707966
Publication Date:
2017-11-28T01:25:30Z
AUTHORS (21)
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.
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