July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Photoreceptor glucose metabolic modulation by adiponectin prevents hyperglycemic ROP
Author Affiliations & Notes
  • Zhongjie Fu
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Chatarina Lofqvist
    Section for Ophthalmology, Department of Clinical Neuroscience and rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, , University of Gothenburg, Göteborg, Sweden
  • Raffael Liegl
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Zhongxiao Wang
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Ye Sun
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Yan Gong
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Chi-Hsiu Liu
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Bertan Cakir
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Rubi Duran
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Alexander Poblete
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Steve S Cho
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • James D Akula
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Michael Kinter
    Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma city, Oklahoma, United States
  • Saswata Talukdar
    Merck Research Laboratories, Merck, Boston, Massachusetts, United States
  • Ann Hellstrom
    Section for Ophthalmology, Department of Clinical Neuroscience and rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, , University of Gothenburg, Göteborg, Sweden
  • Lois E. H. Smith
    Department of Ophthalmology, Children's Hosp Boston/Harvard Med Sch, Brookline, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Zhongjie Fu, None; Chatarina Lofqvist, None; Raffael Liegl, None; Zhongxiao Wang, None; Ye Sun, None; Yan Gong, None; Chi-Hsiu Liu, None; Bertan Cakir, None; Rubi Duran, None; Alexander Poblete, None; Steve Cho, None; James Akula, None; Michael Kinter, None; Saswata Talukdar, None; Ann Hellstrom, None; Lois Smith, None
  • Footnotes
    Support  Blind Children's Center one-year seed grant
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 764. doi:
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      Zhongjie Fu, Chatarina Lofqvist, Raffael Liegl, Zhongxiao Wang, Ye Sun, Yan Gong, Chi-Hsiu Liu, Bertan Cakir, Rubi Duran, Alexander Poblete, Steve S Cho, James D Akula, Michael Kinter, Saswata Talukdar, Ann Hellstrom, Lois E. H. Smith; Photoreceptor glucose metabolic modulation by adiponectin prevents hyperglycemic ROP. Invest. Ophthalmol. Vis. Sci. 2018;59(9):764.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Hyperglycemia is a novel risk factor for retinopathy of prematurity (ROP) but its impact is understudied as the animal model of oxygen-induced retinopathy lacking the hyperglycemic aspect. Photoreceptors are metabolically active and their energy need drives uncontrolled vessel growth. We investigated if hyperglycemia affected photoreceptor metabolism to inhibit neurovascular development, and if adiponectin (APN) restored retinal metabolism to prevent ROP.

Methods : To induce hyperglycemia, C57BL/6J (WT) and APN-deficient (Apn-/-) mouse pups were treated with streptozotocin (STZ) from postnatal day (P) 1 to P9. Blood glucose, serum APN and insulin levels were measured at P10 (n=4-7). Retinal vascular network were quantified (n=17-27) and retinal function was assessed with electroretinogram (ERG, n=7-12). Retinal neurons were isolated by laser-captured microdissection (LCM) and expression of APN receptors was examined (n=3). Retinal metabolic enzymes were quantified by proteomics (n=6). Oxygen consumption rate (OCR, mitochondrial activity) in 661W and hyperglycemic retinas was measured by Seahorse analysis (n=9). Photoreceptor-specific knockdown of PDGFB was achieved by AAV2-RK-shPdgfb. Both male and female pups were used. t test, or ANOVA was used for statistical analysis.

Results : In STZ-treated WT mice, higher blood glucose (P<0.0007), APN (P<0.0001), and lower insulin (P=0.0311) levels were observed. Hyperglycemia delayed deep retinal vascular growth (P<0.001) and attenuated retinal function (rod ERG: P<0.001; cone ERG: P=0.0354). In Apn-/- vs WT mice, deep retinal vessel growth was further inhibited (P=0.0267 in number of meshes, P=0.0300 in total vessel length). APN administration in STZ-induced WT mice restored deep retinal vessel growth (P<0.0001 in number of meshes, P=0.0006 in total vessel length) and retinal function (rod ERG: P<0.01; cone ERG: P=0.0235). APN receptor AdipoR1 was dominantly expressed in photoreceptors. APN deficiency reduced retinal metabolic enzyme levels in glucose metabolism and mitochondrial activity. Activation of the APN pathway increased OCR of hyperglycemic retinas and 661W (P<0.05). Blockade of mitochondrial respiration abolished Pdgfb induction in 661W. Photoreceptor-knockdown of Pdgfb delayed retinal vascular formation.

Conclusions : Modulation of photoreceptor metabolism by APN may suppress early ROP in premature infants.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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