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Photoreceptor glucose metabolism determines normal retinal vascular growth

Fu, Zhongjie; Löfqvist, Chatarina A.; Liegl, Raffael; Wang, Zhongxiao; Sun, Ye; Gong, Yan; Liu, Chi Hsiu; Meng, Steven S.; Burnim, Samuel B. and Arellano, Ivana, et al. (2018) In EMBO Molecular Medicine 10(1). p.76-90
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... (More)

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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published
subject
keywords
Adiponectin, Hyperglycemia, Metabolism, Photoreceptor, Retinopathy of prematurity
in
EMBO Molecular Medicine
volume
10
issue
1
pages
76 - 90
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • scopus:85035152453
ISSN
1757-4676
DOI
10.15252/emmm.201707966
language
English
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yes
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32be2c0f-0c86-443d-bda7-a4e125241ffe
date added to LUP
2017-12-11 13:14:25
date last changed
2018-03-13 03:00:11
@article{32be2c0f-0c86-443d-bda7-a4e125241ffe,
  abstract     = {<p>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.</p>},
  author       = {Fu, Zhongjie and Löfqvist, Chatarina A. and Liegl, Raffael and Wang, Zhongxiao and Sun, Ye and Gong, Yan and Liu, Chi Hsiu and Meng, Steven S. and Burnim, Samuel B. and Arellano, Ivana and Chouinard, My T. and Duran, Rubi and Poblete, Alexander and Cho, Steve S. and Akula, James D. and Kinter, Michael and Ley, David and Pupp, Ingrid Hansen and Talukdar, Saswata and Hellström, Ann and Smith, Lois Eh},
  issn         = {1757-4676},
  keyword      = {Adiponectin,Hyperglycemia,Metabolism,Photoreceptor,Retinopathy of prematurity},
  language     = {eng},
  number       = {1},
  pages        = {76--90},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {EMBO Molecular Medicine},
  title        = {Photoreceptor glucose metabolism determines normal retinal vascular growth},
  url          = {http://dx.doi.org/10.15252/emmm.201707966},
  volume       = {10},
  year         = {2018},
}