β-amyloid expression in age-related cataract lens epithelia and the effect of β-amyloid on oxidative damage in human lens epithelial cells

Aβ and APP expression levels exhibited differential changes during the development of ARC, indicating active feedback of this protein processing. Decreased expression of physiologically generated Aβ in the early and mid-stages of ARC development might be one of the potential mechanisms accelerating oxidative stress in HLECs during cataractogenesis.

Specimens of lens epithelia and aqueous humor were obtained from 255 cataract surgery patients and 48 healthy donor eyes. The ARC samples were divided into four groups according to the Lens Opacities Classification System III, with increasing severity from Group I to Group IV. The HLECs were cultured under healthy or oxidative conditions with or without Aβ pretreatment. Western blot, immunofluorescence, real-time PCR, and enzyme-linked immunosorbent assay were performed to detect Aβ and β-amyloid precursor protein (APP) expression. β-secretase activity was analyzed in lens epithelia and HLECs. The effect of Aβ on the viability of HLECs under oxidative conditions was investigated using a cell viability assay.

To evaluate the changes in β-amyloid (Aβ) expression in age-related cataract (ARC) lens epithelia and the effect of Aβ on oxidative damage in human lens epithelial cells (HLECs).

Compared with the healthy group, the Aβ 1-42 expression levels in lens epithelia and Aβ 1-40 expression levels in aqueous humor decreased in Groups I, II, and III (p<0.05) but were unchanged in Group IV. In contrast, APP expression levels increased in Groups I, II, and III (p<0.05) compared with those in the healthy group but were unchanged in Group IV. H2O2-treated HLECs exhibited decreased amounts of Aβ 1-42 and increased amounts of APP. β-secretase activity decreased in the lens epithelia of all four subgroups of ARCs compared with that in the lens epithelia of healthy subjects and decreased in H2O2-treated HLECs. Furthermore, treatment with nanomolar concentrations (0.2 nM to 10 nM) of Aβ could protect cell viability from oxidative damage. Conclusions: Aβ and APP expression levels exhibited differential changes during the development of ARC, indicating active feedback of this protein processing. Decreased expression of physiologically generated Aβ in the early and mid-stages of ARC development might be one of the potential mechanisms accelerating oxidative stress in HLECs during cataractogenesis.