The role of plasmalemma vesicle-associated protein (PLVAP) in endothelial cells of Schlemm's canal and ocular capillaries

• Published in: Experimental eye research 2012-12, Vol.105, p.27-33
• Main Authors: Herrnberger, Leonie, Ebner, Kathrin, Junglas, Benjamin, Tamm, Ernst R.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Animals; aqueous humor; Aqueous Humor - physiology; Biomarkers - metabolism; Capillaries; Carrier Proteins - physiology; Endothelial Cells - metabolism; fenestrated capillaries; Fluorescent Antibody Technique, Indirect; Humans; Membrane Proteins - physiology; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Middle Aged; outflow; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; PV-1; Retinal Vessels - metabolism; Retinal Vessels - ultrastructure; Schlemm's canal; Sclera - metabolism; Sclera - ultrastructure; Swine
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2012.09.011

Plasmalemma vesicle-associated protein (PLVAP, PV-1) is an endothelial protein that specifically localizes to diaphragms of fenestrae in fenestrated capillaries, and to stomatal diaphragms of caveolae. Here we investigated the localization of PLVAP in Schlemm's canal endothelium and ocular capillaries, and studied the structural effects of PLVAP deficiency. In mouse, pig and human eyes, immunoreactivity for PLVAP was present in fenestrated capillaries of choroid and ciliary processes, but not in the continuous capillaries of retina and ciliary muscle. In all three species staining for PLVAP was seen in the endothelia of the outflow vessels of aqueous humor e.g. Schlemm's canal (SC, mouse and human), aqueous plexus (AP, pig) and the scleral collector channels. Essentially comparable findings were observed when the expression of β-galactosidase was investigated in mutant heterozygous and homozygous PLVAP-deficient mice with LacZ inserted into the Plvap locus. By transmission electron microscopy, the vast majority of caveolae in SC endothelial cells showed a stomatal diaphragm. In addition, solitary fenestrae or minipores with a diaphragm were occasionally observed in SC or AP of all three species. In contrast, mutant Plvap−/− mice showed a complete absence of stomatal diaphragms in SC caveolae while no SC minipores were observed. Moreover, diaphragms were absent in fenestrae of endothelial cells in the capillaries of the ciliary processes or the choriocapillaris, findings which were associated with a substantial decrease in the number of fenestrae. PLVAP is expressed in endothelial cells of Schlemm's canal and is essential for the formation of diaphragms in vascular endothelial cells of the eye. ► Plasmalemma vesicle-associated protein (PLVAP) is expressed in Schlemm's canal endothelium. ► Schlemm's canal endothelium forms caveolae and minipores with diaphragms. ► Diaphragms are absent in PLVAP-deficient mice strongly indicating that PLVAP is an essential structural requirement.