알쯔하이머병 모델 쥐의 망막색소상피에서 아밀로이드 베타 42의 세포 내 발현에 관한 연구

Abstract

Purpose: The expression of amyloid beta 42 in the retina of transgenic mice with 5 familial autosomal dominant mutations (5xFAD) mice (Alzheimers disease mouse model) and the role of amyloid beta 42 on tight junction of retinal pigmented epithelium will be investigated.

Methods: The retina of 5xFAD +/- mice (Tg6799) at post-natal 6, 8 months were investigated. Hematoxylin-eosin stained sections were examined for retinal pathologic changes in 5xFAD mice. With immunofluorescence (IF), the retinal pigment epithelium (RPE) expression of amyloid beta 42 and tight junction markers including occludin, zonular occludens (ZO)-1 were studied in the retina of 5xFAD mice and ARPE-19 cells. Cell viability was determined by the MTT assay in ARPE-19 cells with exogenous 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, especially intracellular expression. ZO-1 expression was markedly decreased, but occludin expression was not changed significantly in RPE of 5xFAD mice. Exogenous OAβ-42 could be uptaken in RPE cells in culture without cell death, subsequently induced breakdown of ZO-1, not occludin.

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