Modulation of the tight junction permeability in cultured retinal epithelial cells

Abstract

A retinal pigment epithelial cell culture model has been established to study blood-retinal barrier function at the RPE cell level. Two diseaserelated blood-retinal barrier conditions, PVR and inherited retina dysfunction in RCS rat, have been modeled in this RPE cell culture to examine the regulation of tight junction barrier. In the modeling of PVR, we have found that serum contains a factor( s) that inhibits tight junction formation as manifested by reduced TER levels in RPE cell culture. More interestingly, we have found that the tight junctions that are inhibited by serum exhibit a fragmented 20-1 labelling pattern. Furthermore, the fragmented 20-1 labelling indu~ed by serum is associated with reduced amounts of the .tight junction protein; 20-1. The active factor in serum has heparin affinity, is heat stable, specific to apical side of the RPE cells, ·and probably biggE;3r than 50 kD.· In the studies of RPE barrier function in RCS rats, interestingly, we have found that RPE cells· from dystrophic rats have the potential to form tight junctions like those from riormal rats. However, the stability of tight junctions can be only supported by normal retina-conditioned medium but not by the dystrophic retina-conditioned medium. This suggests that normal retina releases trophic factors to support tight junctions of RPE cells and that dystrophic retina either loses the trophic factor or produces negative factor to weaken the tight junction stability. These results not only help us understand the regulation of tight junction in specific diseased conditions but also provide information to the general mechanisms of blood-retinal barrier or blood brain-barrier regulation. In future studies, it would be interesting to find the similarity or the differences between the tight junction breakdown induced by serum factor and by the dystrophic retina-conditioned medium.