Abstract
Purpose:
Interferon alpha-2a has been reported to be effective for the treatment of macular edema secondary to uveitis. However, the mechanisms underlying this effect are not completely understood. Our hypothesis is that this cytokine may play a role in the regulation of blood retinal barrier permeability. The aim of our study was to assess the effects of Interferon alpha-2a on the expression of Zonula Occludens-1 and Occludin in ARPE-19 cells.
Methods:
ARPE-19 cells were exposed to vascular endothelial growth factor on the one hand and were cultured in hypoxic conditions in the other hand (hyperpermeability models). Expression of Zonula Occludens-1 and Occludin was assessed by immunochemistry studies and by real time PCR in both situations (1.VEGF treatment and 2. hypoxic conditions) before and after exposing the cells to Interferon alpha-2a.
Results:
Immunochemistry studies: vascular endothelial growth factor decreased the expression of Occludin and Zonula Occludens-1 (p<0.001 and p<0.001); hypoxia did the same (p<0.001 and p<0.001); Interferon alpha -2a increased the expression of Occludin in both hyperpermability models (p<0.001 and p<0.001). However, we did not observe any effect on Zonula Occludens-1 expression (p=0.14 and p=0.32). Real time PCR studies: VEGF decreased the expression of Occludin and Zonula Oclucdens-1 (p=0.012 and p=0.03); hypoxia did the same (p=0.006 and p=0.013); Interferon alpha -2a increased the expression of Occludin in both hyperpermability models (p=0.02 and p=0.01). However, we did not observe any effect on Zonula Occludens-1 expression (p=0.26 and p=0.19).
Conclusions:
Interferon alpha-2a increases the expression of Occludin, an important component of the tight junctions, in ARPE-19 cells. An increased expression of Occludin may contribute to decrease permeability through the outer blood retinal barrier. Our findings provide a rationale for using this cytokine as a therapeutical option in uveitic macular edema.
Keywords: 688 retina •
490 cytokines/chemokines •
555 immunomodulation/immunoregulation