Expression of primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 in cells of the blood aqueous barrier.

Abstract

Purpose: This study focuses on the expression profiling of the primary angle closure glaucoma (PACG) susceptibility gene, Pleckstrin homology-like domain family A member 7 (PLEKHA7) that is important for recruitment and stability of adherens and tight junctions proteins. To investigate PLEKHA7 role in maintaining the junctional barriers within the blood aqueous barrier, we sought to characterize the expression of PLEKHA7 in cells and tissues of the blood aqueous barrier.

Methods: Expression of PLEKHA7 within different tissues of the anterior segment was examined by quantitative real-time PCR. Focusing on the blood vessels, PECAM-1 served as a marker for staining endothelial cells of blood vessels in immunohistochemistry. To ascertain the localisation of PLEKHA7, at cell-cell junctions of the blood aqueous barrier cells with respect to known apical junctional complex markers, we examined the expression of ZO-1 (tight junction) and β-catenin (adherens junction) against PLEKHA7 specific antibody by confocal immunofluorescent analyses of the anterior segment sections of the eye.

Results: PLEKHA7 mRNA was expressed in the iris, ciliary body, trabecular meshwork and optic nerve. Positive PLEKHA7 staining at the endothelium of iris and ciliary body capillaries corresponded to the endothelial marker, PECAM-1 staining profile. PLEKHA7 colocalized with ZO-1 (tight junction) and β-catenin (adherens junction) at blood aqueous barrier sites such as the intercellular clefts of the iris and ciliary body capillaries, iris posterior epithelium and non-pigmented ciliary epithelium.

Conclusions: The expression of PLEKHA7 at apical junction complexes of blood aqueous barrier cells, imply that a compromised permeability at the level of the BAB could be a component of PACG pathogenesis.

Keywords: 533 gene/expression • 446 cell adhesions/cell junctions • 599 microscopy: light/fluorescence/immunohistochemistry