Increased local expression of P-glycoprotein on CD4+ T-cells in vitreous of patients with non-infectious uveitis: a pilot study.

Nearly a third of uveitis patients are unable to achieve adequate inflammation control with conventional anti-inflammatory therapy. Several factors are known to influence responsiveness to anti-inflammatory therapy. In this pilot study, we have investigated the local expression of P-glycoprotein, an efflux-transport protein with role in multi-drug resistance, in vitreous CD4+ T-cells of patients with non-infectious uveitis (NIU). CD4+ T-cells were isolated from vitreous and peripheral venous blood samples of NIU patients undergoing therapeutic vitrectomy. Rhodamine-123, a substrate of P-glycoprotein, whose retention inside cells is inversely proportional to P-glycoprotein function, was used to assay this transporter protein. In addition, cells were stained with IFN-γ, IL-17, GM-CSF and FoxP3, and analysed by flow cytometry. T-cell mitochondria were imaged by Mitotracker Red and confocal microscopy. Vitreous CD4+ T-cells expressed significantly higher P-gp and pro-inflammatory (IL-17+, IFNγ+IL17+) cytokine expression than matching blood samples. Mitochondrial fission was noted in vitreous T-cells and fusion in blood. We concluded that NIU is associated with higher P-glycoprotein expression and pro-inflammatory state in vitreous than in blood. This supports P-glycoprotein inhibition and adjunctive local anti-inflammatory treatment in management of NIU.