DiMattio J
Department of Physiology and Biophysics, New York University School of Medicine, New York.
Invest Ophthalmol Vis Sci. 1992 Sep;33(10):2926-35.
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 14C-AA, 3H-L-glucose (L-glu), and 14C-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, greater than 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 KEi, 0.693 +/- 0.062 [n = 12]; midterm drug-induced diabetes Ki, 0.192 +/- 0.054 [n = 10]; t-test P less than 0.001). The passive L-glu entry rate increased (control KEi, 0.0268 +/- 0.0053 [n = 12]; midterm drug-induced diabetes KEi, 0.0421 +/- 0.075 [n = 10]; t-test P less than 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 KSi, 0.0116 +/- 0.021 [n = 12]; midterm drug-induced diabetes KSi, 0.0136 +/- 0.034 [n = 10]; t-test P less than 0.05). In addition, AA entry rate into lens cortex increased fourfold (control KSi, = 0.0018 +/- 0.0003 [n = 12]; midterm drug-induced diabetes KSi, 0.0081 +/- 0.024 [n = 10]; t-test P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
房水和眼内组织（包括晶状体）中高浓度的抗坏血酸（AA）被认为可以抵御涉及氧气及其自由基的光化学和环境氧化反应的有害影响。此外，AA可能具有多种代谢功能，包括眼内组织中结构性胶原蛋白的形成。最近的研究表明，在豚鼠中，还原型AA集中在房水和晶状体上皮中。这些体内研究扩展到链脲佐菌素诱导的糖尿病大鼠和豚鼠，以探究糖尿病晶状体中AA转运和被动L-葡萄糖移动的状态。在时间零点向血液中注射一剂放射性标记的测试分子，包括14C-AA、3H-L-葡萄糖（L-葡糖）和14C-3-O-甲基-D-葡萄糖，然后在这些标记分子进入房水、晶状体上皮和囊膜以及内部腔室时，测定其随时间变化的浓度。这些动力学研究提供了对正常和糖尿病动物原位被动和载体转运机制功能状态的独特测量。糖尿病动物（血糖大于300mg/dl）根据统一监测的药物诱导糖尿病的时间长短分为短期（10 - 20天）、中期（40 - 60天）和长期（100天以上）。在大鼠晶状体上皮中，AA的主动转运显著下降（对照组KEi为0.693±0.062[n = 12]；中期药物诱导糖尿病组Ki为0.192±0.054[n = 10]；t检验P＜0.001）。被动L-葡糖进入率增加（对照组KEi为0.0268±0.0053[n = 12]；中期药物诱导糖尿病组KEi为0.0421±0.075[n = 10]；t检验P＜0.005）。因此，有人提出药物诱导的糖尿病大鼠晶状体上皮将AA浓缩至高水平的能力有所丧失，上皮中的水平仅为房水的一到两倍；对照动物在20分钟内将AA浓缩至房水的五到八倍。相比之下，L-葡糖从上皮到基质的移动速率增加极小（对照组KSi为0.0116±0.021[n = 12]；中期药物诱导糖尿病组KSi为0.0136±0.034[n = 10]；t检验P＜0.05）。此外，AA进入晶状体皮质的速率增加了四倍（对照组KSi = 0.0018±0.0003[n = 12]；中期药物诱导糖尿病组KSi为0.0081±0.024[n = 10]；t检验P＜0.001）。（摘要截选至400字）
