期刊
EMBO MOLECULAR MEDICINE
卷 10, 期 1, 页码 76-90出版社
WILEY
DOI: 10.15252/emmm.201707966
关键词
adiponectin; hyperglycemia; metabolism; photoreceptor; retinopathy of prematurity
资金
- NIH [EY024864, EY017017, P30AG050911]
- BCH IDDRC [1U54HD090255]
- Lowy Medical Research Institute
- European Commission FP7 project [305485 PREVENT-ROP]
- Swedish Research Council (DNR) [2011-2432]
- Gothenburg County Council [ALFGBG-426531]
- European Commission [305485 PREVENT-ROP (VINNOVA 2009-01152)]
- Swedish Research Council [2014-3140 PREVENT-ROP]
- Harold Hamm Diabetes Center at the University of Oklahoma
- Knights Templar Eye Foundation [76293]
- Blind Children's Center [89282]
- Deutsche Forschungsgemeinschaft (DFG) [Li2650/1-1]
- Boston Children's Hospital OFD/BTREC/CTREC Faculty Career Development Grant
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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