April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Retinal Neurodegeneration in Alzheimer's Disease - Novel in vivo Assessment of Triple Transgenic Model
Author Affiliations & Notes
  • M. F. Cordeiro
    Glaucoma & Retinal Neurodegeneration Research Group,
    UCL Institute of Ophthalmology, London, United Kingdom
    Western Eye Hospital, Imperial Heathcare Trust London, United Kingdom
  • L. Guo
    Glaucoma & Retinal Neurodegeneration Research Group,
    UCL Institute of Ophthalmology, London, United Kingdom
  • K. M. Coxon
    Glaucoma & Retinal Neurodegeneration Research Group,
    UCL Institute of Ophthalmology, London, United Kingdom
  • J. Duggan
    Glaucoma & Retinal Neurodegeneration Research Group,
    UCL Institute of Ophthalmology, London, United Kingdom
  • S. Nizari
    Glaucoma & Retinal Neurodegeneration Research Group,
    UCL Institute of Ophthalmology, London, United Kingdom
  • E. M. Normando
    Glaucoma & Retinal Neurodegeneration Research Group,
    UCL Institute of Ophthalmology, London, United Kingdom
  • S. L. Sensi
    Molecular Neurology Unit, Center of Excellence on Aging (CeSi) University ‘G. d’Annunzio’, Chieti, Italy
  • F. W. Fitzke
    Visual Neurosciences,
    UCL Institute of Ophthalmology, London, United Kingdom
  • T. E. Salt
    Visual Neurosciences,
    UCL Institute of Ophthalmology, London, United Kingdom
  • S. E. Moss
    Cell Biology,
    UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  M.F. Cordeiro, patent application, P; L. Guo, None; K.M. Coxon, None; J. Duggan, None; S. Nizari, None; E.M. Normando, None; S.L. Sensi, None; F.W. Fitzke, None; T.E. Salt, None; S.E. Moss, patent application, P.
  • Footnotes
    Support  The Wellcome Trust
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3843. doi:
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      M. F. Cordeiro, L. Guo, K. M. Coxon, J. Duggan, S. Nizari, E. M. Normando, S. L. Sensi, F. W. Fitzke, T. E. Salt, S. E. Moss; Retinal Neurodegeneration in Alzheimer's Disease - Novel in vivo Assessment of Triple Transgenic Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3843.

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

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Abstract

Purpose: : The triple transgenic AD model (3xTg-AD) is an increasingly used model of Alzheimer’s Disease (AD) which is unique in exhibiting both Abeta and tau neuropathology. Despite the growing evidence of retinal involvement in AD, the 3xTg-AD model has not until now been ophthalmically investigated. Here, we examine the retina of 3xTg-AD mice in vivo, and assess patterns of retinal nerve cell death

Methods: : ,3xTg-AD (4 eyes, 14 months) and control PS1KI (2 eyes, female 18 months) mice were given IR-labelled annexin (1ml, 0.25 mg/ml, Annexin-IR for apoptosis) and Propidium Iodide (1ml, 0.4 mg/ml, PI) intravitreally. Some eyes were additionally assessed after inducing oxidative stress using intravitreal phorbol myristate acetate (1 ml, 10 mg/ml PMA). Imaging was performed using the fluorescein angiogram (488 nm argon laser) and indocyanine green (IR 790 nm diode laser) settings on a modified cSLO (Heidelberg Retina Angiograph 2). Dual-color images (red (PI) and green (IR annexin) channels of an RGB colour image) were obtained and analysed using ImageJ software with specific plugins for co-localisation (JaCoP and Intensity Correlation Analysis).

Results: : All eyes showed the presence of apoptosis. However, quantification of co-localisation showed significantly more RGCs in the early phase of apoptosis (P<0.05, annexin only staining ) and relatively fewer necrotic cells (P<0.05, PI staining only) in the 3xTg-AD model compared with control. In PMA treated eyes, there were significant levels of increased early apoptosis (P<0.05) and decreased late apoptosis (P<0.05, annexin and PI staining) in the 3xTg-AD model. PMA also increased the level of early apoptosis in aged control animals (P<0.05), although not to the same extent (30.3% in aged control as opposed to 61.4% in 3xTg-AD).

Conclusions: : We demonstrate for the first time and in vivo, retinal pathology in the 3xTg-AD. We also show that although a low level of apoptotic and necrotic cell death occurs as a correlate of normal healthy ageing in mice, in AD mice, there is a significant increase in the relative numbers of RGCs in early-phase apoptosis. Furthermore, our results with PMA suggest that AD susceptibility to oxidative stress is increased compared to age-matched controls. We believe the retina provides an ideal tool for the quantitative monitoring of disease mechanisms and dynamics in experimental neurodegeneration.

Keywords: apoptosis/cell death • neuro-ophthalmology: diagnosis • imaging/image analysis: non-clinical 
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