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Michael Hung Ngo, Johane M Robitaille, Christopher R McMaster, shelby steele, Tenille Fleishhacker, jason Berman; A role for the VE-cadherin complex in childhood blinding disorders. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3113. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Vascular-endothelial cadherin (VE-cadherin), encoded by CDH5, is a major adhesion molecule in endothelial adherens junctions, and is an essential component in vasculogenesis. We sought to determine the role of VE-cadherin in retinal vascular development, and assess its capacity to integrate with the FZD4/LRP5/TSPAN12 signaling complex, a known regulator of retinal vascular development
Transgenic zebrafish with fluorescently labeled vasculature were injected with control or cdh5 morpholinos and at four days poster-fertilization retinas were imaged using confocal microscopy. The ability of VE-cadherin to interact with LRP5 was assessed by immunoprecipitation assays and the effect of VE-cadherin on the FZD4/LRP5/TSPAN12 signaling was assessed using a Topflash assay in HEK293 cells.
The cdh5 morphants had an obvious defect in branching of retinal vessels, and had smaller eyes, compared with control morphant zebrafish. The cdh5 morphants also displayed reduced integrity with no distinct vessel wall. VE-cadherin was shown to interact with LRP5 by and to decrease the FZD4/LRP5/TSPAN12 signaling.
We identify VE-cadherin as a component required for vascularization of the peripheral retina. Impaired function of cdh5 can lead to visual complications, likely via its interaction and regulation of the FZD4/LRP5/TSPAN12 signaling complex.
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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