Expression of Amyloid Beta 42 in RPE of Alzheimer Disease Mouse Model

Abstract

Purpose: : To investigate the expression of amyloid beta 42 in the retina of 5xFAD mice (Alzheimer disease mouse model) and the role of amyloid beta 42 on tight junction of retinal pigmented epithelium.

Methods: : The retina of 5xFAD +/- mice (Tg6799) at post-natal 8 months was investigated. Hematoxylin-eosin stained sections were examined for retinal pathologic changes. With immunohistochemistry(IHC) and immunofluorescence(IF), the retinal pigment epithelium (RPE) expression of amyloid beta 42 and tight junction markers, such as occludin, zonular occludens (ZO)-1 were studied. Cell viability was determined by MTT assay in ARPE-19 cells with treatment of oligomeric amyloid beta 42 (OAβ-42). Western blot analysis for occludin, ZO-1 was also performed with treatment of OAβ-42.

Results: : Amyloid beta 42 was mainly expressed in the RPE layer of 5xFAD +/- mice (Tg6799). Both occluding and ZO-1 expressions were markedly decreased in RPE of 5xFAD mice. Tight junction marker expression (occluding, ZO-1) was also significantly attenuated with treatment of OAβ-42 without cell death in ARPE-19 cells.

Conclusions: : Our data suggest that amyloid beta 42 was expressed in the RPE layer of 5xFAD mice of Alzheimer disease mouse model. Amyloid beta 42 could play a role in the breakdown of tight junction of RPE in 5xFAD mice. 5xFAD mice could be used as a animal model for study the relationship between Alzheimer disease and age-related macular degeneration.

Keywords: retinal pigment epithelium • transgenics/knock-outs • immunohistochemistry