Photoreceptor glucose metabolism determines normal retinal vascular growth

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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.; 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.

I: EMBO Molecular Medicine, Vol. 10, Nr. 1, 01.2018, s. 76-90.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Fu, Z, Löfqvist, CA, Liegl, R, Wang, Z, Sun, Y, Gong, Y, Liu, CH, Meng, SS, Burnim, SB, Arellano, I, Chouinard, MT, Duran, R, Poblete, A, Cho, SS, Akula, JD, Kinter, M, Ley, D, Pupp, IH, Talukdar, S, Hellström, A & Smith, LE 2018, 'Photoreceptor glucose metabolism determines normal retinal vascular growth', EMBO Molecular Medicine, vol. 10, nr. 1, s. 76-90. https://doi.org/10.15252/emmm.201707966

APA

Fu, Z., Löfqvist, C. A., Liegl, R., Wang, Z., Sun, Y., Gong, Y., ... Smith, L. E. (2018). Photoreceptor glucose metabolism determines normal retinal vascular growth. EMBO Molecular Medicine, 10(1), 76-90. https://doi.org/10.15252/emmm.201707966

CBE

Fu Z, Löfqvist CA, Liegl R, Wang Z, Sun Y, Gong Y, Liu CH, Meng SS, Burnim SB, Arellano I, Chouinard MT, Duran R, Poblete A, Cho SS, Akula JD, Kinter M, Ley D, Pupp IH, Talukdar S, Hellström A, Smith LE. 2018. Photoreceptor glucose metabolism determines normal retinal vascular growth. EMBO Molecular Medicine. 10(1):76-90. https://doi.org/10.15252/emmm.201707966

MLA

Vancouver

Author

Fu, Zhongjie ; Löfqvist, Chatarina A. ; Liegl, Raffael ; Wang, Zhongxiao ; Sun, Ye ; Gong, Yan ; Liu, Chi Hsiu ; 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. / Photoreceptor glucose metabolism determines normal retinal vascular growth. I: EMBO Molecular Medicine. 2018 ; Vol. 10, Nr. 1. s. 76-90.

RIS

TY - JOUR

T1 - Photoreceptor glucose metabolism determines normal retinal vascular growth

AU - Fu, Zhongjie

AU - Löfqvist, Chatarina A.

AU - Liegl, Raffael

AU - Wang, Zhongxiao

AU - Sun, Ye

AU - Gong, Yan

AU - Liu, Chi Hsiu

AU - Meng, Steven S.

AU - Burnim, Samuel B.

AU - Arellano, Ivana

AU - Chouinard, My T.

AU - Duran, Rubi

AU - Poblete, Alexander

AU - Cho, Steve S.

AU - Akula, James D.

AU - Kinter, Michael

AU - Ley, David

AU - Pupp, Ingrid Hansen

AU - Talukdar, Saswata

AU - Hellström, Ann

AU - Smith, Lois Eh

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

KW - Adiponectin

KW - Hyperglycemia

KW - Metabolism

KW - Photoreceptor

KW - Retinopathy of prematurity

U2 - 10.15252/emmm.201707966

DO - 10.15252/emmm.201707966

M3 - Article

VL - 10

SP - 76

EP - 90

JO - EMBO Molecular Medicine

T2 - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4684

IS - 1

ER -