| Prolonged hyperglycemia resulting from diabetes mellitus or experimental galactosemia may induce disorders in the microvascular structures of the body (kidney, nerves and retina), including retinopathy. Alternatively, retinopathy may be initiated by another metabolic abnormality that is characteristic of diabetes. Glutathione, an important intra-retinal antioxidant, decreases in both of the above mentioned conditions. Additionally, a lethal gamma-glutamyl transferase-deficiency causes mice to develop cataracts within one week of birth. Glutathione peroxidase and glutathione reductase (antioxidant enzymes which act on glutathione) and gamma-glutamyl transferase, which plays an important role in both the synthesis and degradation of glutathione, have been found within the neural retina as well as the retinal pigment epithelium. Activities of these enzymes are known to be influenced by hyperglycemia. Acetazolamide, a known renal gamma-glutamyl transferase inhibitor, was demonstrated to inhibit retinal gamma-glutamyl transferase, and was used to create a gamma-glutamyl transferase-deficient rat. Further, within the retina, gamma-glutamyl transferase was the only glutathione-related antioxidant enzyme that demonstrated decreased activities when compared between control, diabetic, insulin and galactose-fed treatment groups, supporting the hypothesis that gamma-glutamyl transferase is a consequential enzyme in hyperhexosemia, and may be the missing link between hyperhexosemia and the development of retinopathy. |
