Purpose: It has been reported that the accumulation of amyloid β 1–42 (Aβ 1–42) 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 Aβ 1–42 accumulation in lenses.

Methods: 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; Aβ 1–42 levels were analyzed by an ELISA method.

Results: 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 Aβ 1–42, amyloid precursor proteins (APP), β-(BACE1), and· γ-secretase (PS) rise in the lenses of OLETF rats with age; high Aβ 1–42 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 Aβ 1-42 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 Aβ 1-42 protein levels, were significantly higher under high glucose conditions (20 mM) than under normal glucose conditions (5.6 mM).

Conclusions: High glucose leads to the increased expression of genes related to Aβ production, resulting in the accumulation of Aβ in the lens.