June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Shear stress governs choroidal endothelial cell proliferation and homeostasis
Author Affiliations & Notes
  • Bradley D Gelfand
    Ophthalmology, University of Virginia, Charlottesville, Virginia, United States
    Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States
  • Senyou An
    Mechanical Engineering, Indiana-University Purdue-University Indianapolis, Indianapolis, Indiana, United States
    Science and Technology Department, China University of Petroleum (Huadong), Qingdao, China
  • Whitney Yu
    Mechanical Engineering, Indiana-University Purdue-University Indianapolis, Indianapolis, Indiana, United States
  • Rou Chen
    Mechanical Engineering, Indiana-University Purdue-University Indianapolis, Indianapolis, Indiana, United States
  • Jun Yao
    Science and Technology Department, China University of Petroleum (Huadong), Qingdao, China
  • Jayakrishna Ambati
    Ophthalmology, University of Virginia, Charlottesville, Virginia, United States
  • Footnotes
    Commercial Relationships   Bradley Gelfand, None; Senyou An, None; Whitney Yu, None; Rou Chen, None; Jun Yao, None; Jayakrishna Ambati, Allergan (C), Allergan (R), Inflammasome Therapeutics (S), iVeena (Holdings, Delivery Systems, Pharmaceuticals) (S), Olix (C), Olix (R)
  • Footnotes
    Support  American Heart Association 13SDG16770008
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1102. doi:
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    • Get Citation

      Bradley D Gelfand, Senyou An, Whitney Yu, Rou Chen, Jun Yao, Jayakrishna Ambati; Shear stress governs choroidal endothelial cell proliferation and homeostasis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1102.

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

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Abstract

Purpose : The choroidal vascular network provides critical trophic support for the avascular outer retina, and therefore is indispensable for vision. Hemodynamic wall shear stress (WSS), the mechanical drag imparted on vascular endothelium arising from blood flow, has profound effects on the physiology of endothelial cells from different vascular beds, including retinal endothelial cells. However, the magnitude of WSS in the choroid and extent to which endothelial cells of the choroid respond to physiologic WSS are unknown.

Methods : Choroidal shear stress was quantified by computational fluid dynamic modeling of 3D reconstructions of normal human inner choroid using InVascular, which integrates mesoscale modeling with GPU (Graphic Processing Units) parallel computing to achieve fast and reliable numerical results. Physiologic WSS (0-11 dyne/cm2) was applied to primary and immortalized choroidal endothelial cells with an orbital shaker and parallel plate cell culture system for durations ranging from 10 min to 72 h. Functional responses to WSS including morphologic orientation, proliferation and apoptosis were measured by morphometry and flow cytometry. Mitogen-activated protein kinase phosphorylation and expression of KLF2 were measured by western blotting. CD59 abundance was measured by quantitative PCR and western blotting. Deposition of the membrane attack complex (MAC) was measured by stimulation with human serum.

Results : The human inner choroid experiences a wide range of hemodyanmic WSS. Choroidal endothelial cells exhibited alterations in morphology, MAPK signaling and KLF2 expression in response to shear stress. WSS also profoundly inhibited choroidal endothelial cell proliferation in a dose-dependent manner. WSS reduced CD59 expression and increased susceptibility to MAC deposition.

Conclusions : These findings suggest that WSS is a biologically relevant stimulus that elicits morphological and homeostatic changes in choroidal endothelial cells, and may be an important parameter to understand the biology of the choroidal endothelium in health and disease.

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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