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Soojin Kim, Jun Hyeong Park, Young Hee Yoon, Jae-young Koh, Junyeop Lee; Endothelial heterogeneity in the inner and outer blood-retinal barrier. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1893 – A0022.
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The blood-retinal barrier (BRB) has two components: inner and outer barrier. The neurovascular unit of the retina plays key roles in the inner BRB. Choroid, the major components of the outer BRB provides oxygen and nourishment to the retina. Retinal and choroidal blood vessels come in different morphologies and have distinct organotypic characteristics that enable them to execute tissue–specific functions. In this study, we investigated endothelial heterogeneity across the distinct vascular beds in the eye.
We evaluated molecular and functional differences between primary human retinal endothelial cells (HRECs) and human choroidal endothelial cells (HCECs) in terms of angiogenic and vasculogenic properties, permeability, and transcytosis. We performed tube formation assay, cell migration assay, in vitro permeability assay, microfluidic sprouting assay, and transcriptome analysis.
HRECs showed higher proliferation and migration activity than HCECs, but the tube formation ability did not show a significant difference. HCECs displayed earlier sprouting angiogenesis but the overall speed was faster and more stable in HRECs under angiogenic stimuli. HRECs expressed higher adherens junctional proteins than HCECs, but the tight junctional genes and transcytosis related genes were more in HCEC. Angiopoietin-2 was predominantly expressed in HRECs, but VEGF receptors were higher in HCECs. PDGFB was higher in HRECs than HCECs which correlates to the less pericytes coverage in choroidal blood vessels. Our data indicate that HCECs is a quiescent endothelium but can be stimulated under the angiogenic environment, and have a specialized transcriptome for trans-endothelial molecular transport.
Retinal and choroidal blood vessels constitute two distinct BRBs under the endothelial heterogeneity: The outer BRB, size-selective barrier with vascular transcytosis for metabolic support, and the inner BRB, forming tight barriers, composes organotypic vasculature and maintains homeostasis in the eye.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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