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Excessive hydrogen peroxide enhances the attachment of amyloid β1-42 in the lens epithelium of UPL rats, a hereditary model for cataracts.

Abstract：

:Several studies have reported that hydrogen peroxide (H2O2) is related to the toxicity of amyloid β (Aβ), and that the accumulation of Aβ in the lenses of humans causes lens opacification. In this study, we investigate the accumulation of Aβ1-42 in the lenses of UPL rats, which then leads to lens opacification. In addition, we demonstrate the effect of disulfiram eye drops (DSF), a potent radical scavenger, on Aβ1-42 accumulation in the lenses of UPL rats. The H2O2 levels in 46- to 60-day-old UPL rat lenses are significantly higher than in normal rats, and the Aβ1-42 levels in 53- and 60-day-old UPL rats are also increased only in lens epithelium containing capsules (capsule-epithelium), not in the lens cortex and nucleus. However, no increases in amyloid precursor protein (APP), β- or γ-secretase mRNA were observed in lenses of the corresponding ages. It has been thought that Aβ1-42 that accumulates in the lenses of UPL rats is actually produced in another tissue containing neuronal cells, such as brain or retina. Aβ1-42 levels in the brain and retina rise with aging, and the levels of APP, β- and γ-secretase mRNA in the retinas of 53-day-old UPL rats with opaque lenses are significantly higher than in 25-day-old UPL rats with transparent lenses. In contrast to the results in retinas, the levels of APP, β- and γ-secretase mRNA in the brains of 25- and 53-day-old UPL rats are similar. On the other hand, in an in vitro study, Aβ1-42 attachment in the lens capsule-epithelium of UPL rats was found to increase in H2O2. In addition, in an in vivo study, the inhibition of H2O2 by DSF was found to attenuate the increase in Aβ1-42 in the lens capsule-epithelium of 60-day-old UPL rats. Taken together, we hypothesize that excessive H2O2 in the lens enhances the attachment of Aβ1-42 in the lens capsule-epithelium of UPL rats, and that the instillation of DSF has the ability to attenuate the attachment of Aβ1-42 by inhibiting H2O2 production in lens. These findings provide significant information that can be used to design further studies aimed at developing anti-cataract drugs.

journal_name

Toxicology

journal_title

Toxicology

authors

Nagai N,Ito Y

doi

10.1016/j.tox.2013.08.003

subject

Has Abstract

pub_date

2014-01-06 00:00:00

pages

55-64

eissn

0300-483X

issn

1879-3185

pii

S0300-483X(13)00213-8

journal_volume

315

pub_type

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Excessive hydrogen peroxide enhances the attachment of amyloid β1-42 in the lens epithelium of UPL rats, a hereditary model for cataracts.