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M. Shimazawa, Y. Inokuchi, T. Okuno, G. Sakaguchi, A. Kato, T. Sugiyama, T. Kudo, T. Ikeda, M. Takeda, H. Hara; Involvement of Amyloid-ß in Retinal Function. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1302. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To clarify whether amyloid-ß (Aß) protein participated in retinal function and cell death using three types of transgenic (Tg) mice: human mutant amyloid precursor protein (APP) Tg (Tg 2576), mutant presenilin-1 (PS-1) knockin, and APP/PS-1 double Tg mice.
APP and Aß proteins in retinal extracts or specimens were determined with an ELISA assay or immunostaining. Retinal damage was induced by intravitreal injection of N-methyl-d-aspartate (NMDA) at 5 nmol. NMDA receptor 1 (NR1) subunit and phosphorylated form (Thr286) of calcium/calmodulin-dependent protein kinase IIα (p-CaMKIIα) were measured in retinal extracts and specimens using an immunoblotting and immunostaining. Electroretinogram (ERG) was recorded from APP/PS-1 Tg and their wild-type mice.
Insoluble form of Aß1-40 was significantly increased in retina of APP and APP/PS-1, but not PS-1 Tg mice, as compared with that of their wild-type mice. Immunostaining revealed the accumulation of intracellular Aß1-42 in retinal ganglion cells, inner nuclear layer and outer nuclear layer of APP Tg mice and APP/PS-1 Tg mice. Interestingly, APP and APP/PS-1 Tg mice, but not PS-1 Tg mice, had smaller NMDA-induced retinal damage than their wild-type mice, although there were no histological differences in non-treated retina between each Tg mice and wild-type mice. P-CaMKIIα, but not total CaMKIIα or total NR1, was decreased in non-treated retinas of APP/PS-1 Tg mice as compared with those of wild-type mice. Furthermore, NMDA-induced increase of p-CaMKIIα in retina of APP/PS-1 Tg mice was lower than that of wild-type mice. In ERG recordings, latencies of a-wave and oscillation potentials prolonged in APP/PS-1 mice as compared with those of wild-type mice.
These findings suggest that Aß may attenuate activation of NMDA-receptor signaling pathways and retinal function.
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