Glucose transport in the bovine ciliary body epithelium (CBE)

Doctoral thesis English OPEN
Chan, Chu Yan

Diabetic patients are prone to develop cataract, compared to non-diabetic patients (Kyselova et al., 2004). The global prevalence of diabetes is around 150 millions in 2004 (5% of the world population), with 1.8 million people in the United Kingdom affected (Diabetes UK, 2004). In western countries, diabetes accounts for around 12% of the total cataract population (Harding, 1999). It has been proposed that hyperglycemia is the major risk factor in diabetic cataract, and could be the starting point for all of the consequent pathological changes including, glucoxidation, glycation and activation of the polyol pathway, which finally result in diabetic complications (Sensi et al., 1995 Hotta, 1997 Brownlee, 2001). The present study aimed to characterise the mechanism of glucose transport into the aqueous humour. Using the Ussing-type chamber technique, glucose transport kinetics were characterised for the bovine CBE. The glucose fluxes were sensitive to a number of glucose transporter inhibitors including cytochalasin B ( 80% inhibition), phloretin ( 59% inhibition) and phlorizin ( 21% inhibition), and it also varied with stromal glucose concentration. In an investigation of mRNA expression using RT-PCR, GLUT1, GLUT3, GLUT4, GLUT5 and SGLT2 were found to be expressed in the bovine CBE. Due to difficulties encountered in the protein expression study, it was not possible to confirm that all of these mRNAs are translated. Nevertheless, the major glucose transport mechanism across the bovine CBE was determined to be a facilitative and carrier-mediated mode, since the glucose transport was effectively inhibited by the addition of cytochalasin B and phloretin. The transport system is likely to saturate when the plasma glucose concentration reaches 10.6 mM. These results, together with the gene expression data, may provide a new insight into devising a therapeutic strategy in the control of aqueous glucose levels which may eventually prevent the diabetic cataract formation.
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