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Bradley Gelfand, Jayakrishna Ambati, Senyou An, Rou Chen, Whitney H Yu, Jun Yao; Hemodynamic shear stress in the inner choroid primes endothelium for complement damage. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3473. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Disorders of the choroidal circulation are an etiologic element of many ophthalmic pathologies, including myopia, diabetic choroidopathy, polypoidal choroidal vasculopathy, and age-related macular degeneration (AMD). We developed a numerical modeling approach to calculate hemodynamics in realistic, human-derived three-dimensional geometries of the inner choroid. One biologically important relevant hemodynamic parameters is wall shear stress (WSS), which is the mechanical drag experienced by all vascular endothelium as a consequence of blood flow. WSS has profound effects on the physiology of endothelial cells from different vascular beds. However, the magnitude of WSS in the choroid and extent to which endothelial cells of the choroid respond to physiologic WSS are unknown.
Human donor eyes were processed to generate a realistic 3D anatomic reconstruction of the inner choroidal circulation. Choroidal hemodynamic parameters were then quantified by computational fluid dynamic modeling using InVascular, a custom numerical modeling software package. 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.
Analysis of a cohort of human donor eyes, we found that hemodynamic parameters (velocity, pressure) exhibit remarkable variability within lobular structures of choriocapillaris. The distribution of WSS exhibited striking heterogeneity within the choriocapillaris plane, with local maxima located near arteriole inlets. In response to WSS stimulation in vitro, choroidal endothelial cells exhibited profound alterations in morphology, proliferation, and susceptibility to oxidative stress. WSS also rendered choroidal endothelial cells susceptible to MAC deposition in a dose-dependent manner. WSS reduced surface expression of the complement regulator CD59 via membrane shedding. In human choroid, MAC deposition positively correlated with calculated WSS.
Collectively, our work reveals the distribution of hemodynamic parameters in realistic human inner choroid, and identify WSS as an important environmental cue governing homeostasis of inner choroidal endothelium.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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