Kanth Vangipurapu Rajani, Lavanya Katikala, Srinivas Jayanthi, Raju Turlapati Naga
Department of Zoology, Osmania University, Hyderabad 500 007, India.
Curr Eye Res. 2009 Apr;34(4):274-81. doi: 10.1080/02713680902725954.
Glycated lens proteins are capable of producing reactive oxygen species (ROS), which, in turn, can oxidize tryptophan (Trp) into kynurenines. Indoleamine 2,3-dioxygenase (IDO), which is expressed in many tissues and which is inducible by interferon-gamma (IFN-gamma), is able to oxidize Trp into kynurenines. These kynurenines can modify lens proteins and, in fact, kynurenine adducts are markedly increased in lenses with age-related nuclear cataract. Therefore, it has been suggested that lenticular IDO is involved in diabetic cataractogenesis. The aim of the present study was to examine the possible role(s) of IDO in streptozotocin (STZ)-induced diabetic cataract in rats.
Diabetic cataract was induced in male Wistar-NIN rats by IP injection of STZ (34 mg/kg body wt). Slit lamp biomicroscopy was used to monitor progression of the resulting hyperglycemia-induced cataract. Treated and control rats were sacrificed at 30 and 60 days, at which times changes in lenticular levels of IDO activity, IDO mRNA, IFN-gamma mRNA (IDO inducer), Trp, kynurenic acid (KYNA), oxidative stress markers (malondialdehyde and carbonyls), antioxidant (reduced glutathione), antioxidant enzymes (glutathione peroxidase and superoxide dismutase), and polyol enzymes (aldose reductase and sorbitol dehydrogenase) were determined and compared.
Cataract was observed to begin at 30 days after STZ treatment, and mature cataract was observed 60 days after STZ treatment. Lenticular levels of IDO activity, IDO mRNA, IFN-gamma mRNA, Trp, and KYNA increased significantly at 30 days and remained elevated through 60 days. Significant increases were also observed in levels of oxidative stress markers, antioxidant enzymes, and polyol enzymes at 30 and 60 days after STZ treatment. However, the level of reduced GSH decreased by approximately 50% at both points of determination.
Production of IDO was induced in STZ-induced diabetic cataractous lenses, possibly by locally produced IFN- gamma. IDO-mediated oxidation of Trp may partly explain the increase in lens KYNA and may thus be implicated in cataractogenesis in concert with the non-enzymic oxidation of Trp by glycated lens proteins.
糖化晶状体蛋白能够产生活性氧（ROS），而ROS又可将色氨酸（Trp）氧化为犬尿氨酸。吲哚胺2,3-双加氧酶（IDO）在许多组织中表达，且可被γ-干扰素（IFN-γ）诱导，它能够将Trp氧化为犬尿氨酸。这些犬尿氨酸可修饰晶状体蛋白，事实上，在年龄相关性核性白内障晶状体中，犬尿氨酸加合物显著增加。因此，有人提出晶状体IDO参与糖尿病性白内障的发生。本研究的目的是探讨IDO在链脲佐菌素（STZ）诱导的大鼠糖尿病性白内障中可能发挥的作用。
通过腹腔注射STZ（34 mg/kg体重）诱导雄性Wistar-NIN大鼠患糖尿病性白内障。使用裂隙灯生物显微镜监测由此产生的高血糖诱导性白内障的进展。在30天和60天时处死治疗组和对照组大鼠，此时测定并比较晶状体中IDO活性、IDO mRNA、IFN-γ mRNA（IDO诱导剂）、Trp、犬尿酸（KYNA）、氧化应激标志物（丙二醛和羰基）、抗氧化剂（还原型谷胱甘肽）、抗氧化酶（谷胱甘肽过氧化物酶和超氧化物歧化酶）以及多元醇酶（醛糖还原酶和山梨醇脱氢酶）水平的变化。
观察到白内障在STZ治疗后30天开始出现，在STZ治疗后60天出现成熟白内障。晶状体中IDO活性、IDO mRNA、IFN-γ mRNA、Trp和KYNA水平在30天时显著升高，并在60天时持续升高。在STZ治疗后30天和60天，氧化应激标志物、抗氧化酶和多元醇酶水平也显著升高。然而，在两个测定点，还原型谷胱甘肽水平均下降了约50%。
在STZ诱导的糖尿病性白内障晶状体中，IDO的产生可能是由局部产生的IFN-γ诱导的。IDO介导的Trp氧化可能部分解释了晶状体中KYNA的增加，因此可能与糖化晶状体蛋白对Trp的非酶促氧化协同参与白内障的发生。
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