Varma Shambhu D, Kovtun Svitlana, Hegde Kavita
Department of Ophthalmology and Visual Sciences, University Of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mol Vis. 2010 Dec 8;16:2626-33.
The primary objective of the study was to investigate the possible inhibition of cataract formation by topical administration of caffeine using the galactosemic rat model. It was hypothesized that caffeine will do so by acting as scavenger of reactive oxygen species known to be generated under hyperglycemic conditions.
Cataract was induced by feeding young rats a diet containing 24% galactose for a period of 25 days. A control group of such rats was treated with a placebo eye drop preparation containing hydroxy propyl methyl cellulose as a wetting agent. In the experimental group, the rats were treated with the above preparation mixed with 72 mM caffeine.
Administration of caffeine eye drops was found to significantly inhibit the onset as well as the progress of cataract formation. By day 25 on the galactose diet, all the animals in the control group developed advanced white opacity spread over the entire area of the lens. In the caffeine group, the formation of such opacity remained strikingly inhibited. The lenses remained largely transparent. The transparency data paralleled the higher concentration of glutathione maintained by caffeine treatment. Its levels in the placebo group were 0.8, 0.5, and 0.4 µmoles/g lens wt. on days 5, 15, and 25 against a consistent basal control value of ~3 µmoles/g over the entire period. In the caffeine group, the corresponding values were nearly 3 µmoles/g till day 15, but decreasing to ~2 µmoles/g on day 25. The levels were hence significantly higher than in the caffeine untreated group, remaining relatively closer to the basal controls. In addition, the compound was found effective in inhibiting morphological changes induced by galactose.
Micromolar amounts of topical caffeine have been found to be significantly effective in inhibiting the formation of galactose cataract, strongly suggesting its possible usefulness against diabetic cataracts. The effects are attributed to its ability to prevent oxidative stress and consequent maintenance of tissue metabolic and transport functions, in addition to preventing the induction of apoptosis.
本研究的主要目的是利用半乳糖血症大鼠模型，研究局部应用咖啡因对白内障形成的可能抑制作用。研究假设是，咖啡因将通过作为已知在高血糖条件下产生的活性氧清除剂来发挥作用。
通过给幼鼠喂食含24%半乳糖的饮食25天来诱导白内障。一组这样的大鼠作为对照组，用含有羟丙基甲基纤维素作为湿润剂的安慰剂眼药水制剂进行治疗。在实验组中，大鼠用上述制剂与72 mM咖啡因混合进行治疗。
发现给予咖啡因眼药水可显著抑制白内障形成的起始和进展。在半乳糖饮食喂养25天时，对照组的所有动物晶状体整个区域都出现了进展性白色混浊。在咖啡因组中，这种混浊的形成仍受到显著抑制。晶状体在很大程度上保持透明。透明度数据与咖啡因治疗维持的较高谷胱甘肽浓度平行。在第5天、第15天和第25天，安慰剂组中其水平分别为0.8、0.5和0.4微摩尔/克晶状体重量，而在整个期间基础对照值始终约为3微摩尔/克。在咖啡因组中，直到第15天相应值接近3微摩尔/克，但在第25天降至约2微摩尔/克。因此，这些水平显著高于未用咖啡因处理的组，相对更接近基础对照值。此外，发现该化合物可有效抑制半乳糖诱导的形态学变化。
已发现微摩尔量的局部咖啡因在抑制半乳糖性白内障形成方面具有显著效果，强烈表明其对糖尿病性白内障可能有用。这些作用归因于其预防氧化应激以及随之维持组织代谢和转运功能的能力，此外还能预防细胞凋亡的诱导。
