High ascorbic acid (AA) levels in the aqueous humor and intraocular tissues, including the lens, are thought to protect against the harmful effects of photochemical and ambient oxidation reactions involving oxygen and its radicals. In addition, AA may have various metabolic functions, including structural collagen formation in intraocular tissues. Recent work showed that, in the guinea pig, reduced AA was concentrated in the aqueous and lens epithelium. These in vivo studies were extended to streptozotocin-induced diabetic rats and guinea pigs to explore the state of AA transport and passive L-glucose movement in the diabetic lens. A bolus dose of radiolabeled test molecules, including C-14-AA, H-3-L-glucose (L-glu), and C-14-3-O-methyl-D-glucose, was injected into the blood at time zero, and the time-dependent concentrations of these labeled molecules were determined as they move into the aqueous humor, lens epithelium and capsule, and interior compartments. These kinetic studies provided a unique measurement of the functioning state of passive and carrier transport mechanisms in situ in normal and diabetic animals. Diabetic animals (blood glucose, > 300 mg/dl) were categorized in terms of the length of time of uniform monitored drug-induced diabetes as short term (10-20 days); midterm (40-60 days), and long term (100+ days). In the rat lens epithelium, significant decrease occurred in the active movement of AA (control K(Ei), 0.693 +/- 0.062 [n = 12]; midterm drug-induced diabetes K(i), 0.192 +/- 0.054 [n = 10]; t-test P < 0.001). The passive L-glu entry rate increased (control K(Ei), 0.0268 +/- 0.0053 [n = 12]; midterm drug-induced diabetes K(Ei), 0.0421 +/- 0.075 [n = 10]; t-test P < 0.005). Thus, it was suggested that the drug-induced diabetic rat lens epithelium had lost some of its ability to concentrate AA to high levels and achieved epithelial levels only one- to twofold those of aqueous; control animals concentrated AA to levels of five- to eightfold those of aqueous within 20 min. By contrast, the rate of movement of L-glu from epithelium to stroma increased minimally (control K(Si), 0.0116 +/- 0.021 [n = 12]; midterm drug-induced diabetes K(Si), 0.0136 +/- 0.034 [n = 10]; t-test P < 0.05). In addition, AA entry rate into lens cortex increased fourfold (control K(Si) = 0.0018 +/- 0.0003 [n = 12]; midterm drug-induced diabetes K(Si), 0.0081 +/- 0.024 [n = 10]; t-test P < 0.001). Therefore, more AA leaves the epithelium and moves into the lens interior. Experiments with diabetic guinea pigs demonstrated a diminished ability to bring AA into the aqueous humor and in concentrating AA in lens epithelium. Thus, in both species, these data showed that the ability to bring AA actively into the lens epithelium was compromised by diabetes and that AA moved more readily into diabetic lens cortex. With the high glucose level and lower lens metabolism, this may have harmful consequences.
