The Effects of Bisphosphonates on Taurine Transport in Retinal Capillary Endothelial Cells Under High Glucose Conditions - Advances in Experimental Medicine and Biology - page 60

200

* **

180

160

* **

***

140

***

*

120

*

100

80

60

40 Alendronate

Pamidronate

20

0

0 1 2 3 4 5 6

Pre-incubation time (h)

Fig. 7.2 Per-incubation time dependency of bisphosphonates on [ 3 H]taurine uptake by TR-iBRB
cells in high glucose condition (25 mM). The cells were pretreated with 10 mM alendronate or
pamidronate for 0.5, 4, 6 h. [ 3 H]taurine uptake was performed with ECF buffer containing [ 3 H]
taurine (28 nM) for 5 min at 37°C. Each point represents the mean ± SEM ( n = 4). * p < 0.05;
*** p < 0.001, signi fi cantly different from control

7.4 Discussion

In the present study, we used TR-iBRB cells as an in vitro iBRB model. TR-iBRB
cell lines, conditionally immortalized rat retinal capillary endothelial cell lines, have
been established by transfecting the retrovirus vector-encoded temperature-sensitive
(ts) simian virus (SV) 40 large T-antigen (Hosoya et al. 2001 ). These cell lines are
good in vitro model for various endogenous and exogenous compound transport to
the retina and as a screening tool for drugs which might be capable of delivery to the
retina (Terasaki and Hosoya 2001 ). RT-PCR and immunoblot analysis showed that
TauT is expressed in rat retina and TR-iBRB cells (Tomi et al. 2007 ) .
Taurine is well known to act as an antioxidant and osmolyte. In diabetic state,
elevated glucose level will obviously disturb cellular osmoregulation. Actually, the
changes in taurine transporter activities have been reported in streptozotocin (STZ)-
induced diabetic rats, human retinal pigment epithelial cells by high glucose, and
diabetic neuropathy models (Stevens et al. 1999 ). Our results also revealed sup-
pressed [ 3 H]taurine uptake in TR-iBRB cells under high glucose condition for 48 h
(Fig. 7.1 ). In vitro exposure to high glucose has been shown to rapidly increase
VEGF expression in various cell types and tissues (Natarajan et al. 1997 ) , which
may account for the elevated VEGF in the retina of humans and animals with dia-
betes (Mathews et al. 1997 ; Gilbert et al. 1998 ). Schrufer et al. have recently found
that hyperglycemia increases expression of VEGF in retinal Müller cells in vitro