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Mahdy Ranjbar, Jan-Niklas Stutzer, Heidrun L Deissler, Salvatore Grisanti; Effects of BIBF1120 on inner and outer blood-retinal barrier permeability. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5303. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
VEGFA plays a major role in various pathologies concerning the inner and outer retinal barrier, but involvement of other growth factors, i.e. bFGF or PDGF, and their receptors has been suggested. Herein, we evaluated the effects of BIBF1120, a triple angiokinase inhibitor, on blood-retinal barrier permeability in vitro.
After treating confluent immortalized bovine retinal endothelial cells (iBREC) and human retinal pigment epithelial cells (ARPE19) with 50ng/mL (1.3nM) VEGFA for 24h, BIBF1120 was added at 10nM (→inhibiting VEGF-R2) or at 100nM (→inhibiting VEGF-R1/2, FGF-R1/2/3, PDGF-Rα/β). The cell index (CI) as a measure of permeability was monitored by continuous electric cell-substrate impedance measurements (xCELLigence). Presence of tight-junction proteins (TJPs) was also assessed.
VEGFA induced a biphasic reduction of CI of iBREC, but not of ARPE19. BIBF1120 (10 and 100nM) completely reverted VEGFA-induced drop of CI of iBREC and even at 10nM significantly increased VEGFA-induced loss of TJPs . CI of ARPE-19 was not affected by BIBF1120 in the presence or absence of VEGFA.
BIBF1120 showed a positive impact on inner blood-retinal barrier permeability and might be considered for therapy of diseases like diabetic macular edema and macular edema secondary to retinal vein occlusion.
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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