Liu Haitao, Tang Jie, Lee Chieh Allen, Kern Timothy S
Case Western Reserve University, Cleveland, Ohio, United States The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Case Western Reserve University, Cleveland, Ohio, United States.
Invest Ophthalmol Vis Sci. 2015 Jan 8;56(1):647-53. doi: 10.1167/iovs.14-15220.
l-Methylfolate, pyridoxal 5'-phosphate, and methylcobalamin, individually have been reported to have beneficial effects on diabetes-induced defects. The possibility that combining these therapeutic approaches might have additional benefit led us to investigate the effect of Metanx against development of early stages of diabetic retinopathy in a mouse model.
C57BL/6J mice were made diabetic with streptozotocin, and some were given Metanx (a combination food product) mixed in the food at a dose of 5 mg/kg of body weight. Mice were killed at 2 months and 10 months of study for assessment of retinal function, retinal vascular histopathology, accumulation of albumin in neural retina, and biochemical and physiological abnormalities in retina.
Two months of diabetes significantly increased leukostasis within retinal vessels and superoxide generation by the retina. Diabetes also significantly increased expression of intercellular adhesion molecule-1 (ICAM-1) and phosphorylation of IκB. Daily consumption of Metanx significantly inhibited all of these abnormalities. Ten months of diabetes significantly increased the degeneration of retinal capillaries and impaired visual function (spatial frequency threshold (SFT) and a parameter of contrast sensitivity) compared to nondiabetic controls. Daily consumption of Metanx for 10 months inhibited impairment of SFT but had no significant beneficial effect on capillary degeneration, pericyte loss, or the estimate of contrast sensitivity.
Metanx inhibited a diabetes-induced defect in retinal spatial frequency threshold and inhibited measures of oxidative stress and inflammation. It had no significant effect on contrast sensitivity or retinal capillary degeneration. Nutritional management with Metanx may help inhibit diabetes-induced defects in visual function.
据报道，左旋甲基叶酸、磷酸吡哆醛和甲钴胺单独使用对糖尿病引起的缺陷具有有益作用。联合使用这些治疗方法可能会带来额外益处，这促使我们在小鼠模型中研究甲钴胺对糖尿病视网膜病变早期发展的影响。
用链脲佐菌素使C57BL/6J小鼠患糖尿病，部分小鼠给予混入食物中的甲钴胺（一种复合食品），剂量为5毫克/千克体重。在研究的2个月和10个月时处死小鼠，以评估视网膜功能、视网膜血管组织病理学、神经视网膜中白蛋白的积累以及视网膜中的生化和生理异常。
糖尿病2个月显著增加了视网膜血管内的白细胞淤滞和视网膜超氧化物的生成。糖尿病还显著增加了细胞间黏附分子-1（ICAM-1）的表达和IκB的磷酸化。每日食用甲钴胺显著抑制了所有这些异常。与非糖尿病对照组相比，糖尿病10个月显著增加了视网膜毛细血管的退化并损害了视觉功能（空间频率阈值（SFT）和对比敏感度参数）。每日食用甲钴胺10个月可抑制SFT的损害，但对毛细血管退化、周细胞丢失或对比敏感度估计没有显著的有益作用。
甲钴胺抑制了糖尿病引起的视网膜空间频率阈值缺陷，并抑制了氧化应激和炎症指标。它对对比敏感度或视网膜毛细血管退化没有显著影响。用甲钴胺进行营养管理可能有助于抑制糖尿病引起的视觉功能缺陷。
