Modulation of RAGE and the downstream targets of RAGE signaling cascades by taurine in Lycium barbarum (Goji Berry) : protection of human retinal pigment epithelial barrier function and its potential benefit in diabetic retinopathy

Background: Retinal pigment epithelial (RPE) barrier disruption is an early event in diabetic retinopathy (DR). However, the biochemical details of its pathophysiology and treatment options are unclear. Taurine is reported to be beneficial in DR and is abundant in the fruit of Lycium barbarum (Goji Berry, LB). Hence, we have investigated the effect of taurine pure compound and an extract of LB extract rich in taurine on a model of DR, the ARPE-19 cell line treated with high glucose, and whether their effects on RPE barrier disruption by glucose may contribute to protection against DR. Methods: The levels of NF-κB and ICAM-1 activity were measured by luciferase reporter gene analysis. Protein levels of RAGE and VEGF were determined by Western blot analysis. VEGF secretion levels were analysed by ELISA. The barrier function was determined by measuring TER and FITC-dextran permeability. Distribution of claudin-1 and connexin 43 proteins was examined by Western blot and immunofluorescence analysis. Results: Taurine and an extract of LB rich in taurine dose-dependently down-regulate increased levels of RAGE, NF-κB, VEGF and ICAM-1 in the ARPE-19 cell line exposed to 33.3 mM glucose. This reversal was associated with attenuation of high glucose-induced RPE barrier disruption, which was shown by increased TER, reduced FITCdextran permeability, characteristic morphological staining and dose-dependent modulation of claudin-1 and connexion 43 protein expression. Conclusions: Pure taurine and LB extract protect against barrier disruption following exposure of ARPE-19 cells to high glucose. These effects are associated with altered NF-κB, ICAM-1 activity and VEGF secretion. Taurine and LB extract decrease RAGE. As they are known to activate PPAR-γ we propose that their effects on barrier disruption may occur through their effects on RAGE and the downstream targets of RAGE signaling cascades. This pathway provides a rationale for the potential of taurine and the LB extract for protection against progression of DR.