Abstract
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-1activity 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 FITC-dextran permeability, characteristic morphological staining and dose-dependent modulation of claudin-1 and connexin 43 protein expression. Conclusions: Puretaurine and LBextractprotect against barrier disruption following exposure of ARPE-19 cells to high glucose. These effects are associated with altered NF-κB, ICAM-1activity 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.
Highlights
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and remains a major cause of preventable blindness worldwide [18]
As hyperglycemia increases expression of the receptor for advanced glycation end products (RAGEs) [66] we determined the effect of Lycium barbarum (LB) extract and taurine on receptor advanced glycation end products (RAGE) protein expression in high glucosetreated ARPE-19 cells
As hyperglycemia activates the pro-inflammatory transcriptional factor, NF-κB [31], we determined the effect of LB extract and taurine on NF-κB luciferase activity in high glucose-treated ARPE-19 cells
Summary
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and remains a major cause of preventable blindness worldwide [18]. Chronic hyperglycemia is believed to be the primary pathogenic factor for inducing damage to pigment epithelial cells [14]. This results in changes to the pattern of production of a number of proinflammatory mediators, followed by angiogenesis in tissue remodeling, and increase in retinal vasopermeability and disruption of the BRB [11,22,64]. Degradation of high glucose-induced RPE cells leads to down-regulation of the gap junction protein connexin 43 and up-regulation of the tight junction protein claudin-1, causing disruption of the epithelial barrier function [1,34]. Retinal pigment epithelial (RPE) barrier disruption is an early event in diabetic retinopathy (DR). 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
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