Page 12 - Y. Vascular biology

[Y. Vascular biology-7]

PLVAP is essential for the maturation and maintenance of

choroidal blood vessels

SOO JIN KIM¹˙³˙#, SANG A. KIM³˙#, YEONG A. CHOI³, YURIM KIM³, YOSHIAKI KUBOTA⁴, GOU YOUNG KOH⁵,
DO YOUNG PARK³, JUNYEOP LEE¹˙²˙*

¹Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea,

²Departement of Opthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505,
Korea, ³Departement of Opthalmology, Yeungnam University College of Medicine, Daegu 42415, Korea,
⁴Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan, ⁵Center for Vascular

Research, Institute for Basic Science (IBS), Daejeon 34126, Korea

Endothelial fenestration is a transvascular channel for exchanging nutrients and metabolites. Plasmalemmal vesicle-

associated protein (PLVAP) forms fenestration and its diaphragm. Here, we investigated the role of PLVAP in
choriocapillaris, a specialized fenestrated capillary in the eye. Tamoxifen-inducible endothelial cell-specific PLVAP

conditional knockout mice (PLVAPiΔEC) showed thickened endothelium and reduced fenestrations by cytoskeleton
rearrangement. Sinusoidal capillaries were dilated and improperly remodeled in PLVAPiΔEC. Ultra-widefield

angiography showed retardation of maturation in retinal and choroidal large vessels often with vascular leakage in
PLVAPiΔEC. The phenotypes were rescued after subretinal injection of plasmid DNA expressing PLVAP. VEGFA was

suppressed in the retinal pigment epithelium (RPE)-choroid in PLVAPiΔEC. As a result, PLVAPiΔEC displayed thin
choroid and irregular RPE basal infoldings, indicating metabolic insufficiency. In human, PLVAP expression was

reduced in aged choroid. Disrupted polarized ultrastructure and consequent outer BRB breakdown in PLVAP
deficiency resembles age-related macular degeneration (AMD). PLVAP is essential for the maturation and

maintenance of choroid and loss of PLVAP could be involved in the pathogenesis of AMD.