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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)
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.
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.
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.
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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