• Biomolecules & Therapeutics
• /
• v.24 no.1
• /
• pp.94-98
• /
• 2016

The objective of the present study was to elucidate the effect of bisphosphonates, anti-osteoporosis agents, on glucose uptake in retinal capillary endothelial cells under normal and high glucose conditions. The change of glucose uptake by pre-treatment of bisphosphonates at the inner blood-retinal barrier (iBRB) was determined by measuring cellular uptake of $[^3H]3$-O-methyl glucose (3-OMG) using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB cells) under normal and high glucose conditions. $[^3H]3$-OMG uptake was inhibited by simultaneous treatment of unlabeled D-glucose and 3-OMG as well as glucose transport inhibitor, cytochalasin B. On the other hand, simultaneous treatment of alendronate or pamidronate had no significant inhibitory effect on $[^3H]3$-OMG uptake by TR-iBRB cells. Under high glucose condition of TR-iBRB cells, $[^3H]3$-OMG uptake was increased at 48 h. However, $[^3H]3$-OMG uptake was decreased significantly by pre-treatment of alendronate or pamidronate compared with the values for normal and high glucose conditions. Moreover, geranylgeraniol (GGOH), a mevalonate pathway intermediate, increased the uptake of $[^3H]3$-OMG reduced by bisphosphonates pre-treatment. But, pre-treatment of histamine did not show significant inhibition of $[^3H]3$-OMG uptake. The glucose uptake may be down regulated by inhibiting the mevalonate pathway with pre-treatment of bisphosphonates in TR-iBRB cells at high glucose condition.

• Biomolecules & Therapeutics
• /
• v.17 no.2
• /
• pp.175-180
• /
• 2009

Taurine is the most abundant free amino acid in the retina and transported into retina via taurine transporter (TauT) at the inner blood-retinal barrier (iBRB). In the present study, we investigated whether the taurine transport at the iBRB is regulated by oxidative stress or disease-like state in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB) used as an in vitro model of iBRB. First, [$^3H$]taurine uptake and efflux by TR-iBRB were regulated in the presence of extracellular $Ca^{2+}$. [$^3H$]Taurine uptake was inhibited and efflux was enhanced under $Ca^{2+}$ free condition in the cells. In addition, oxidative stress inducing agents such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$), lipopolysaccharide (LPS), diethyl maleate (DEM) and glutamate increased [$^3H$]taurine uptake and decreased [$^3H$]taurine efflux in TR-iBRB cells. Whereas, 3-morpholinosydnonimine (SIN-1), which is known to NO donor decreased [$^3H$]taurine uptake. Lastly, TR-iBRB cells exposed to high glucose (25 mM) medium and the [$^3H$]taurine uptake was reduced about 20% at the condition. Also, [$^3H$]taurine uptake was decreased by cytochalasin B, which is known to glucose transport inhibitor. In conclusion, taurine transport in TR-iBRB cells is regulated diversely at extracellular $Ca^{2+}$, oxidative stress and hyperglycemic condition. It suggested that taurine would play a role as a retinal protector in diverse disease states.

• BMB Reports
• /
• v.39 no.4
• /
• pp.339-345
• /
• 2006

The blood-neural barrier (BNB), including blood-brain barrier (BBB) and blood-retinal barrier (BRB), is an endothelial barrier constructed by an extensive network of endothelial cells, astrocytes and neurons to form functional 'neurovascular units', which has an important role in maintaining a precisely regulated microenvironment for reliable neuronal activity. Although failure of the BNB may be a precipitating event or a consequence, the breakdown of BNB is closely related with the development and progression of CNS diseases. Therefore, BNB is most essential in the regulation of microenvironment of the CNS. The BNB is a selective diffusion barrier characterized by tight junctions between endothelial cells, lack of fenestrations, and specific BNB transporters. The BNB have been shown to be astrocyte dependent, for it is formed by the CNS capillary endothelial cells, surrounded by astrocytic end-foot processes. Given the anatomical associations with endothelial cells, it could be supposed that astrocytes play a role in the development, maintenance, and breakdown of the BNB. Therefore, astrocytes-endothelial cells interaction influences the BNB in both physiological and pathological conditions. If we better understand mutual interactions between astrocytes and endothelial cells, in the near future, we could provide a critical solution to the BNB problems and create new opportunities for future success of treating CNS diseases. Here, we focused astrocyte-endothelial cell interaction in the formation and function of the BNB.