Abstract
Purpose: :
The retinal pigment epithelium (RPE) cells play a pivotal role in maintaining the immune privilege of the eye. In patients with exudative macula degeneration, an increased inflammatory activity in choroidal neovascular membranes (CNV) has been reported. Aside from toxic side effects on a variety of cells, little is known on functional changes induced by Bevacizumab. Since Bevacizumab reaches the (RPE), we analyzed a side effect of Bevacizumab on it‘s immunological properties in vitro.
Methods: :
Two human RPE lines (ARPE-19, M154) were used in co-culture experiments with T cells of different donors. Increasing concentrations of Bevacizumab (0.9µg/ml, 0.3µg/ml and 0.1µg/ml, respectively) were added to these co-cultures. After labeling with Carboxyfluoresceinsucciminidylester (CFSE), T cells were stimulated with anti-CD3 and anti- CD28 antibodies. Co-cultured T cells were assayed for proliferation, phenotype (CD25, CD122, CD132) and function (intracellular Interferon gamma (IFN-γ) production). P-values from ANOVA and toukey post-hoc contrasts.
Results: :
T cell proliferation was significantly inhibited by both RPE lines. Addition of Bevacizumab to the co-cultures did not alter the RPE-related inhibitory effect on the proliferation. Neither the phenotype (equal expression of CD25 and reduced CD122 and CD132) nor the functionality (lower IFN-γ production) was changed by adding either of both anti-angiogenic drugs to co-cultures of RPE cell and T cells.
Conclusions: :
The presence of Bevacizumab with RPE cells did not alter its immune regulatory functions. RPE cells did inhibit T cell receptor (TCR) driven proliferation of T cells in the presence of Bevacizumab. A negative side effect following intravitreal injection of Bevacizumab on the immune privileged status of the RPE is therefore unlikely.
Keywords: vascular endothelial growth factor • immune tolerance/privilege • retinal pigment epithelium