March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Role Of Amyloid Precursor Protein In Lipoprotein Deposition From Retinal Pigment Epithelium
Author Affiliations & Notes
  • Rina Sato
    Ophthalmology, Nagoya City Univ Med School, Nagoya, Japan
  • Tsutomu Yasukawa
    Ophthalmology, Nagoya City Univ Med School, Nagoya, Japan
  • Ayae Kubota
    Ophthalmology, Nagoya City Univ Med School, Nagoya, Japan
  • Aki Kato
    Ophthalmology, Nagoya City Univ Med School, Nagoya, Japan
  • Akiko Nishiwaki
    Ophthalmology, Nishiwaki Eye Clinic, Nagoya, Japan
  • Yuichiro Ogura
    Ophthalmology, Nagoya City Univ Med School, Nagoya, Japan
  • Footnotes
    Commercial Relationships  Rina Sato, None; Tsutomu Yasukawa, None; Ayae Kubota, None; Aki Kato, None; Akiko Nishiwaki, None; Yuichiro Ogura, None
  • Footnotes
    Support  2011-2013 Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science, H23-116
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5297. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Rina Sato, Tsutomu Yasukawa, Ayae Kubota, Aki Kato, Akiko Nishiwaki, Yuichiro Ogura; Role Of Amyloid Precursor Protein In Lipoprotein Deposition From Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5297. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Amyloid ß is detectable in drusen in aging eyes and a biomarker in age-related macular degeneration as well as Alzheimer disease. We have previously developed the spheroid culture system of retinal pigment ephthelial (RPE) cells, which might be useful to elucidate unknown basal functions of RPE. The purpose of this study is to clarify the relationship of amyloid ß with lipoprotein deposition from RPE by use of this culture system.

Methods: : Human RPE cells were cultured in medium with methylcellulose on a 96-well round-bottomed culture plate. RPE cells in each well aggregated to form a spheroid, on the surface of which a monolayer of RPE was constructed. The inhibitors of ß-secretase and γ-secretase, which cleave amyloid precursor protein (APP) to amyloid ß and other fragments, were added in the culture medium. A light microscope was used to measure the diameter of spheroids and observe the appearance periodically. Expression of amyloid ß, apoB-100 (a component of RPE-derived lipoproteins), and elastin (a major element of Bruch’s membrane) was evaluated by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA).

Results: : Diameters of spheroids treated with each secretase inhibitor were bigger than those in the control group throughout the observation period. In the groups with secretase inhibition, spheroids had smooth surface and reduced outward deposition of lipoproteins, as compared with the control group. Immunohistochemistry and ELISA showed that expression of apoB-100 and elastin on spheroids as well as amyloid ß was suppressed by each secretase inhibitor.

Conclusions: : The deposition of RPE-lipoproteins and the turnover of Bruch’s membrane as well as the production of amyloid ß were reduced by secretase inhibitors. These results suggested that the cleavage of APP by secretases might play a crucial role in lipoprotein deposition and subsequent subclinical turnover of Bruch’s membrane.

Keywords: age-related macular degeneration • retinal pigment epithelium • drusen 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×