Lizak M J, Mori K, Kador P F
NIH MRI Research Facility, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Ocul Pharmacol Ther. 2001 Oct;17(5):475-83. doi: 10.1089/108076801753266857.
The polyol pathway plays an important role in the formation of diabetic complications of the eye. Due to variations in the pharmacokinetic properties of aldose reductase inhibitors and variations in the degradation of the blood-ocular barrier, it is often difficult to determine the proper intraocular levels of aldose reductase inhibitor required for inhibition of aldose reductase activity in ocular tissues. Utilizing localized magnetic resonance spectroscopy (MRS), the present method can determine adequate inhibition of aldose reductase activity in the lens by noninvasively measuring polyol pathway activity in the eye. New Zealand White rabbits, under anesthesia, were administered an intravitreal injection of 3-fluoro-3-deoxy-D-glucose (3FDG). Localized MRS was then used to assess polyol pathway activity by determining the levels of 3-fluoro-3-deoxy-D-sorbitol (3FS) and 3-fluoro-3-deoxy-D-fructose (3FF) metabolite formation from 3FDG in the eye. MRS was able to follow the loss of 3FDG from the vitreous into the anterior segment of the eye and particularly into the lens and aqueous. The primary metabolism of 3FDG observed by MRS was the formation of 3FS in the lens that is catalyzed by aldose reductase. Production of 3FS was linear in time and decreased with the oral administration of an aldose reductase inhibitor.
多元醇途径在糖尿病眼部并发症的形成中起重要作用。由于醛糖还原酶抑制剂的药代动力学特性存在差异以及血眼屏障的降解存在差异，通常难以确定抑制眼部组织中醛糖还原酶活性所需的醛糖还原酶抑制剂的合适眼内水平。利用局部磁共振波谱（MRS），本方法可通过非侵入性测量眼中的多元醇途径活性来确定晶状体中醛糖还原酶活性的充分抑制。对麻醉状态下的新西兰白兔进行玻璃体内注射3-氟-3-脱氧-D-葡萄糖（3FDG）。然后使用局部MRS通过测定眼中由3FDG形成的3-氟-3-脱氧-D-山梨醇（3FS）和3-氟-3-脱氧-D-果糖（3FF）代谢物水平来评估多元醇途径活性。MRS能够追踪3FDG从玻璃体进入眼前段，特别是进入晶状体和房水的过程。MRS观察到的3FDG的主要代谢是在醛糖还原酶催化下在晶状体中形成3FS。3FS的产生在时间上呈线性，并随着口服醛糖还原酶抑制剂而降低。
