Nagai Noriaki, Ito Yoshimasa, Sasaki Hiroshi
Faculty of Pharmacy Kinki University, Higashi-Osaka, Osaka, Japan.
Department of Ophthalmology, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan.
Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1408-17. doi: 10.1167/iovs.15-19026.
It has been reported that the accumulation of amyloid β1-42 (Aβ1-42) in human lenses can cause some forms of lens opacification. However, the factors leading to changes in the accumulation of Aβ in the lens remain obscure. In this study, we investigate the effect of hyperglycemia on Aβ1-42 accumulation in lenses.
Otsuka Long-Evans Tokushima Fatty (OLETF) rats and the human lens epithelial cell line SRA 01/04 (HLE cells) were used. The expression of mRNA was determined using a quantitative real-time RT-PCR method; Aβ1-42 levels were analyzed by an ELISA method.
Otsuka Long-Evans Tokushima Fatty rats at more than 20 weeks of age develop diabetes mellitus with hyperglycemia. Additionally, the levels of the mRNAs for Aβ1-42, amyloid precursor proteins (APP), β-(BACE1), and·γ-secretase (PS) rise in the lenses of OLETF rats with age; high Aβ1-42 levels are observed in the lens capsule-epithelium and cortex. The enhanced expression of the genes for APP, BACE1, and PS in the lenses of OLETF rats is prevented by food restriction (25 g/d/rat). When the effect of glucose levels on the production of Aβ1-42 was investigated in the human lens epithelial cell line SRA 01/04 (HLE cells), the mRNA levels for APP, BACE1, and PS, as well as Aβ1-42 protein levels, were significantly higher under high glucose conditions (20 mM) than under normal glucose conditions (5.6 mM).
High glucose leads to the increased expression of genes related to Aβ production, resulting in the accumulation of Aβ in the lens.
据报道，淀粉样β1-42（Aβ1-42）在人晶状体中的积累可导致某些形式的晶状体混浊。然而，导致晶状体中Aβ积累变化的因素仍不清楚。在本研究中，我们调查了高血糖对晶状体中Aβ1-42积累的影响。
使用大冢长-艾氏-德岛肥胖（OLETF）大鼠和人晶状体上皮细胞系SRA 01/04（HLE细胞）。使用定量实时RT-PCR方法测定mRNA的表达；通过ELISA方法分析Aβ1-42水平。
20周龄以上的大冢长-艾氏-德岛肥胖大鼠会发展为伴有高血糖的糖尿病。此外，随着年龄增长，OLETF大鼠晶状体中Aβ1-42、淀粉样前体蛋白（APP）、β-分泌酶（BACE1）和γ-分泌酶（PS）的mRNA水平升高；在晶状体囊-上皮和皮质中观察到高Aβ1-42水平。通过食物限制（25 g/d/大鼠）可防止OLETF大鼠晶状体中APP、BACE1和PS基因的表达增强。当在人晶状体上皮细胞系SRA 01/04（HLE细胞）中研究葡萄糖水平对Aβ1-42产生的影响时，高糖条件（20 mM）下APP、BACE1和PS的mRNA水平以及Aβ1-42蛋白水平均显著高于正常糖条件（5.6 mM）。
高糖导致与Aβ产生相关的基因表达增加，从而导致Aβ在晶状体中积累。
