July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Factors of Susceptibility in the Development of Diabetic Retinopathy
Author Affiliations & Notes
  • Ebrahim Abdul Shukkur
    Ophthalmology, Visual & Anatomical Sciences, Wayne State University SOM, Detroit, Michigan, United States
  • Spandana Alluri
    Ophthalmology, Visual & Anatomical Sciences, Wayne State University SOM, Detroit, Michigan, United States
  • Laura Young
    Ophthalmology, Visual & Anatomical Sciences, Wayne State University SOM, Detroit, Michigan, United States
  • Eliisa Strand
    Ophthalmology, Visual & Anatomical Sciences, Wayne State University SOM, Detroit, Michigan, United States
  • David Kracht
    Ophthalmology, Visual & Anatomical Sciences, Wayne State University SOM, Detroit, Michigan, United States
  • Thomas W Carion
    Ophthalmology, Visual & Anatomical Sciences, Wayne State University SOM, Detroit, Michigan, United States
  • Elizabeth A Berger
    Ophthalmology, Visual & Anatomical Sciences, Wayne State University SOM, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Ebrahim Abdul Shukkur, None; Spandana Alluri, None; Laura Young, None; Eliisa Strand, None; David Kracht, None; Thomas Carion, None; Elizabeth Berger, None
  • Footnotes
    Support  Research to Prevent Blindness;
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2663. doi:
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    • Get Citation

      Ebrahim Abdul Shukkur, Spandana Alluri, Laura Young, Eliisa Strand, David Kracht, Thomas W Carion, Elizabeth A Berger; Factors of Susceptibility in the Development of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2663.

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

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Abstract

Purpose : Roughly 1/3 of the 285 million diagnosed diabetics worldwide present with signs of diabetic retinopathy (DR), which is also the leading cause of adult-onset blindness. Despite these staggering statistics, why don’t all diabetics develop DR? The immune response, specifically inflammation, is a well-recognized causal factor in the pathogenesis of retinopathy. To this end, the current project seeks to elucidate innate immune factors and related pathways that confer susceptibility to retinal damage in diabetes.

Methods : Using in vivo and in vitro approaches, we examine hyperglycemia-induced differences between C57BL/6 (B6) (susceptible) and BALB/c (relatively resistant) mice. Comparative proteomics was carried out on STZ-induced diabetic male B6 and BLAB/c mice. Retinal lysates were processed after 2 months of confirmed diabetes. Protein profiles were obtained using 2D gel electrophoresis for total protein and phosphoprotein levels using SyproRubyTM and Pro-QTM Diamond staining, respectively. In addition, human (H) REC were co-cultured with B6- vs. BALB/c-derived neutrophils (PMN) using a flow-based hollow-fiber modeling system. Primary cells were grown as a monolayer using the FiberCell Systems Polysulfone Plus cartridge, then the system was circulated with either normal glucose (NG, 5mM) or high glucose (HG, 25mM) media to acclimate. PMN were then added to the co-culture system and after 28 days of co-culture, cells were assessed for ROS production and membrane potential as detected by flow cytometry using CellROX® Green and Image-iTTM TMRM, respectively.

Results : Our findings indicate clear differences in the response of B6 and BALB/c mice to diabetic conditions. Comparative proteomics have revealed global changes associated with the susceptibility of B6 retinas compared to BALB/c. This is further supported by in vitro results showing that ROS levels were remarkably higher in the B6 co-culture compared to BALB/c – both under normal and high glucose conditions. Furthermore, these increases in ROS correlate with observed decreases in membrane potential in B6 co-cultures; surprisingly, the opposite trend is observed in BALB/c co-cultures.

Conclusions : These results support the premise that innate immune background contributes to disease pathogenesis of DR. We provide insight into the underlying factors driving the observed differences that promote susceptibility in the retinal response to hyperglycemia.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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