June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Hyperglycemia alters VEGF-induced permeability in retinal endothelial cells
Author Affiliations & Notes
  • Maximilian McCann
    Illinois Eye and Ear Infirmary, Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Yueru Li
    Illinois Eye and Ear Infirmary, Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Andrius Kazlauskas
    Illinois Eye and Ear Infirmary, Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
    Department of Physiology & Biophysics, University of Illinois at Chicago, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Maximilian McCann None; Yueru Li None; Andrius Kazlauskas None
  • Footnotes
    Support  T32 HL144459; NIH grant EY031350-01; P30 Core grant (P30 EY001792)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3594 – A0049. doi:
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    • Get Citation

      Maximilian McCann, Yueru Li, Andrius Kazlauskas; Hyperglycemia alters VEGF-induced permeability in retinal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3594 – A0049.

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

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Abstract

Purpose : Although vascular endothelial growth factor (VEGF) drives vascular dysfunction in both non-diabetic (neovascular AMD) and diabetic (DME and PDR) settings, it remains an open question if hyperglycemia (a key element of the diabetic setting) influences VEGF-mediated permeability. The purpose of this study was to begin to address this question.

Methods : We studied the contribution of the renin-angiotensin-aldosterone system (RAAS) to VEGF-induced permeability in primary human retinal endothelial cells (HRECs), which were cultured for 10 days in either normal glucose (NG; 5 mM), or high glucose (HG; 30 mM) media, using transendothelial electrical resistance assay (TEER). Additionally, RNAseq analysis was performed on HRECs cultured in normal and high glucose conditions for 10 days.

Results : RNAseq analysis indicated that HG alone altered expression of over 2000 genes. Furthermore, VEGF altered expression of almost twice as many genes in HG versus NG cells. While many of the VEGF-regulated genes and pathways were unique to one glucose concentration, a small subset was altered by VEGF in both NG and HG cells. Follow-up laboratory-based experiments indicated that these common genes/pathways were probably not governing VEGF-driven permeability. Consequently, we considered if VEGF-mediated permeability was different between NG and HG cells. Indeed, it was. HG cells were more sensitive to VEGF-induced permeability. Furthermore, VEGF-induced permeability was in part dependent on RAAS in HG, but not NG cells. Our ongoing studies are focused on elucidating the underlying mechanism by which RAAS contributes to VEGF-induced permeability.

Conclusions : Hyperglycemia alters the way VEGF induces permeability in retinal endothelial cells. This realization, along with the underlying mechanism of this phenomenon, will guide development of individualized therapeutics for retinopathies in and outside the context of diabetes.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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