May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Involvement of Amyloid-ß in Retinal Function
Author Affiliations & Notes
  • M. Shimazawa
    Department of Biofunctional Molecules, Gifu Pharmaceutical University, Gifu, Japan
  • Y. Inokuchi
    Department of Biofunctional Molecules, Gifu Pharmaceutical University, Gifu, Japan
  • T. Okuno
    Department of Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • G. Sakaguchi
    Discovery Research Laboratories, Shionogi and Co., Ltd., Koka, Japan
  • A. Kato
    Discovery Research Laboratories, Shionogi and Co., Ltd., Koka, Japan
  • T. Sugiyama
    Department of Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • T. Kudo
    Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan
  • T. Ikeda
    Department of Ophthalmology, Osaka Medical College, Takatsuki, Japan
  • M. Takeda
    Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan
  • H. Hara
    Department of Biofunctional Molecules, Gifu Pharmaceutical University, Gifu, Japan
  • Footnotes
    Commercial Relationships M. Shimazawa, None; Y. Inokuchi, None; T. Okuno, None; G. Sakaguchi, None; A. Kato, None; T. Sugiyama, None; T. Kudo, None; T. Ikeda, None; M. Takeda, None; H. Hara, None.
  • Footnotes
    Support Grant-in-Aid for Scientific Research (No. 18659515)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1302. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: 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.

Methods:: 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.

Results:: 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.

Conclusions:: These findings suggest that Aß may attenuate activation of NMDA-receptor signaling pathways and retinal function.

Keywords: retina • phosphorylation • immunohistochemistry 
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