May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Non–Invasive Molecular Imaging of Alzheimer’s Disease ß–Amyloid and Scrapieform Prion Protein (Prpsc) in the Lens
Author Affiliations & Notes
  • J. Moncaster
    Center for Ophthalmic Research, Harvard Medical School/Brigham and Women's Hospital, Boston, MA
  • M. Sadowski
    Dept. of Neurology, New York University Medical School, New York, NY
  • K. O'Rourke
    ARS, ADRU, USDA, Pullman, WA
  • R. Moir
    Genetics & Aging Research Unit, Harvard Medical School/Massachusetts General Hospital, Boston, MA
  • E. Arnett
    Dept. of Biological Structure and Ophthalmology, University of Washington, Seattle, WA
  • J.I. Clark
    Dept. of Biological Structure and Ophthalmology, University of Washington, Seattle, WA
  • L.T. Chylack, Jr.
    Center for Ophthalmic Research, Harvard Medical School/Brigham and Women's Hospital, Boston, MA
  • R. Tanzi
    Genetics & Aging Research Unit, Harvard Medical School/Massachusetts General Hospital, Boston, MA
  • T. Wisniewski
    Dept. of Neurology, New York University Medical School, New York, NY
  • L.E. Goldstein
    Center for Ophthalmic Research, Harvard Medical School/Brigham and Women's Hospital, Boston, MA
  • Footnotes
    Commercial Relationships  J. Moncaster, None; M. Sadowski, None; K. O'Rourke, None; R. Moir, None; E. Arnett, None; J.I. Clark, Neuroptix Corporation, I; Neuroptix Corporation, C; Neuroptix Corporation, P; L.T. Chylack, Neuroptix Corporation, I; Neuroptix Corporation, C; Neuroptix Corporation, P; R. Tanzi, None; T. Wisniewski, None; L.E. Goldstein, Neuroptix Corporation, I; Neuroptix Corporation, C; Neuroptix Corporation, P.
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1978. doi:
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    • Get Citation

      J. Moncaster, M. Sadowski, K. O'Rourke, R. Moir, E. Arnett, J.I. Clark, L.T. Chylack, Jr., R. Tanzi, T. Wisniewski, L.E. Goldstein; Non–Invasive Molecular Imaging of Alzheimer’s Disease ß–Amyloid and Scrapieform Prion Protein (Prpsc) in the Lens . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1978.

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

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Abstract

Purpose: : We have previously identified Aß deposition, amyloid pathology, and co–localizing supranuclear cataracts (SNC) in human AD lenses (Goldstein et al., Lancet, 2003) and in Tg2576 mice (Goldstein et al. [2001] 42: ARVO Abst 1614; Render et al. [2003] 44: ARVO Abst 3063), an established AD mouse model (Hsiao, Science [1996] 274:99). Here we investigate amyloid deposition in ß–amyloid overexpressing transgenic mice and scrapiform prion protein (PrPsc)–infected sheep and mice.

Methods: : Immunohistochemistry/fluorescence, quantitative western blot, SELDI–MS, tryptic digest/MS sequencing, immunogold EM; stereophotomicroscopy. Non–invasive in vivo techniques: static and quasi–elastic light scattering (SLS,QLS).

Results: : We confirm our previously reported ß–amyloid lens pathology in transgenic mice. We demonstrate proteinase K resistant prion protein in the lenses of confirmed PrPsc infected sheep and PrPsc (87v) inoculated mice. Inoculated mice showed morphologically variable SNC phenotypic expression. Non–invasive quantitative in vivo lens analyses were accomplished using static light scattering (SLS, Seeberger et al., J Biomed Opt. [2004] 9:116) and a more sensitive quantitative technique, quasi–elastic light scattering (QLS, Optiscan 1300, Neuroptix, Amherst, MA), both utilized in non–anesthetized animals. Systemic administration of a fluorescent lipophilic amyloid–binding ligand (Me–X04, Klunk et al. J Neuropathol Exp Neurol [2002] 61:797) in 87v PrPsc–inoculated mice resulted in supranuclear Me–X04 binding in vivo. Supranuclear Me–X04 histofluorescence, PrP immunostaining, and amyloid pathology were also observed in ex vivo lens specimens. Preliminary results suggest that PrPsc –related amyloid pathology can be detected non–invasively in the lens.

Conclusions: : Alzheimer's and PrPsc–related amyloid pathology is detectable in the lens in various species.

Keywords: cataract • imaging/image analysis: non-clinical • pathology: experimental 
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