June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Amyloid β enhances expression and activity of HTRA1 in retinal pigment epithelial cells, a mechanism of wet age-related macular degeneration development from drusen
Author Affiliations & Notes
  • Jiying Wang
    Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Tokyo, Japan
  • Kyoko Ohno-Matsui
    Ophthalmology & Visual Sci, Tokyo Medical & Dental Univ, Tokyo, Japan
  • Ikuo Morita
    Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Tokyo, Japan
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 335. doi:
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      Jiying Wang, Kyoko Ohno-Matsui, Ikuo Morita; Amyloid β enhances expression and activity of HTRA1 in retinal pigment epithelial cells, a mechanism of wet age-related macular degeneration development from drusen. Invest. Ophthalmol. Vis. Sci. 2013;54(15):335.

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

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Abstract

Purpose: Single nucleotide polymorphism of high-temperature requirement factor A1 (HTRA1) has been shown strongly associated with increased risk for developing wet age-related macular degeneration (AMD). We have proved previously that amyloid β (Aβ) is a key component of drusen to trigger AMD. In this study, we investigated the effect of Aβ on expression and activity of HTRA1 in retinal pigment epithelial (RPE) cells.

Methods: Primarily cultured human RPE cells were stimulated with 25 μM and 50 μM Aβ for 24 hours. HTRA1 mRNA expression and protein production in the supernatant were analyzed by real-time PCR and western blot. The binding between Aβ and HTRA1 was determined by co-immunoprecipitation. Activity of HTRA1 preincubated with/without 50 μM Aβ for 1 hour was measured by activity assay using β-casein substrate.

Results: Aβ treatment induced a significant dose-dependent increase of HTRA1 mRNA expression and protein production in the supernatant of cultured human RPE cells. Aβ could efficiently bind to HTRA1 in vitro in co-immunoprecipiation analysis. In activity assay, HTRA1 preincubated with Aβ could more intensely degrade β-casein compared to HTRA1 preincubated without Aβ.

Conclusions: These results suggest the mechanism that Aβ accumulated in drusen causes over-expression and enhanced activity of HTRA1 in subretinal space. This phenomenon might be an important process for the development of wet AMD.

Keywords: 695 retinal degenerations: cell biology  
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