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
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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