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Wendy A Dailey, Kenneth P Mitton, Kimberly A Drenser, Michael Thomas Trese; Norrin Counters VEGFA Induced Expression of Transcytosis Marker PLVAP. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3668. doi: https://doi.org/.
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There are two ways in which VEGFA induces endothelial cell permeability and subsequent Blood Retinal Barrier (BRB) breakdown. One is by the depletion of Endothelial cell-to-cell junction proteins (paracellular) and the other is by an increase in transcellular transport, trancytosis. Norrin is a Wnt activating growth factor that stabilizes the BRB. The purpose of this study was to determine the effect of norrin upon VEGFA induced PLVAP expression, a marker of transcytosis.
Human Retinal Microvascular Endothelial Cells (HRMECs) were treated with VEGFA for 24 hours alone or in combination with Norrin. The RNA was then isolated from the cells and converted to cDNA. PLVAP Taqman assays with TBP normalization were then run and the comparative method used for data analysis.
A significant increase in PLVAP expression was seen after treating for 24 hours with high levels (100ng/ml) of VEGFA165 (12X) or its b-isoform (8X). Norrin (200ng/ml) treatment alone significantly decreased PLVAP expression (0.4X). Co-treatment with norrin decreased VEGFA165-b (100ng/ml) induced PLVAP by 30% and VEGFA165-b (25 ng/ml) induced PLVAP by 60%.
Norrin can significantly counter VEGFA induced PLVAP expression. This explains one mechanism of norrin restoration of the BRB in animal models of proliferative retinopathy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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