June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Diabetes hinders resolution of inflammation and reestablishment of the inner blood-retinal barrier following retinal ischemia-reperfusion injury
Author Affiliations & Notes
  • Sumathi Shanmugam
    Ophthalmology and Visual Sciences, University of Mitchigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Cheng-mao Lin
    Ophthalmology and Visual Sciences, University of Mitchigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Dejuan Kong
    Ophthalmology and Visual Sciences, University of Mitchigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Heather Hager
    Ophthalmology and Visual Sciences, University of Mitchigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • David A Antonetti
    Ophthalmology and Visual Sciences, University of Mitchigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Steven F Abcouwer
    Ophthalmology and Visual Sciences, University of Mitchigan, Kellogg Eye Center, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Sumathi Shanmugam, None; Cheng-mao Lin, None; Dejuan Kong, None; Heather Hager, None; David Antonetti, None; Steven Abcouwer, None
  • Footnotes
    Support  R01EY007739, Novo Nordisk Science Forum Award, P30EY007003
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2527. doi:
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      Sumathi Shanmugam, Cheng-mao Lin, Dejuan Kong, Heather Hager, David A Antonetti, Steven F Abcouwer; Diabetes hinders resolution of inflammation and reestablishment of the inner blood-retinal barrier following retinal ischemia-reperfusion injury. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2527.

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

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Abstract

Purpose : Diabetic retinopathy may be caused by an imbalance of retinal damage and repair processes. The mouse intraocular pressure-induced ischemia-reperfusion (IR) model exhibits neurodegeneration, neuroinflammation, leukostasis followed by leukocyte infiltration and vascular permeability; which all normally resolve between 3 and 4 weeks after injury. We utilized the IR model to test the hypothesis that negative effects of diabetes on retinal repair processes impede resolution of inflammation and restoration of the inner blood-retinal barrier (iBRB) following retinal injury.

Methods : IR injury was unilaterally produced by injection of saline into the anterior chamber for 90 min, while contralateral Sham eyes received a needle puncture only. To examine the effects of diabetes, IR injury was produced in control and diabetic mice after 4 weeks of streptozotocin-induced diabetes. Vascular permeability was assayed by measuring the retinal accumulation of circulating FITC-BSA. Retinal microglia and infiltrating leukocytes were quantified by flow cytometry with CD45, CD11b, Ly6C and Ly6G markers. Microglial proliferation and migration was assessed by immunofluorescence of Iba1 and Ki67 antigen in retinal sections.

Results : Whereas IR produced 45% less (p<0.01) vascular leak in diabetics than controls at 2 days following injury, diabetic mice exhibited a 2.4-fold higher (p<0.05) leak at 4 weeks after IR. In normal mice, microglia responded to IR by transiently proliferating and migrating from plexiform layers toward the ganglion cell layer; while infiltrating leukocytes exhibited a temporal progression with granulocytes and Ly6Chi inflammatory monocytes predominating at 1 day and Ly6Cneg reparative monocytes peeking at day 7. There were no significant differences in accumulation of granulocytes or Ly6Chi monocytes between control and diabetic mice. Surprisingly, at 2 weeks following IR diabetic mice exhibited a persistent 2.3-fold increase in microglial population (p<0.01) that was not observed in controls. The numbers of Ly6Cneg monocytes were also more than 2-fold greater (p<0.05) in retinas of diabetic mice at both 2 and 4 weeks following IR.

Conclusions : Lack of iBRB recovery and extended microglial and Ly6Cneg monocyte responses suggests that impaired repair processes can contribute to diabetic retinopathy pathology.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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