July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Age-dependent structural and microvascular changes in retina associated with progressive amyloid-β and Tau deposition in triple transgenic mouse model of Alzheimer’s disease
Author Affiliations & Notes
  • Hossein Nazari Khanamiri
    Ophthalmology, University of Texas Medical Branch, Galveston, Texas, United States
  • Mauro Montalbano
    University of Texas Medical Branch, Galveston, Texas, United States
  • Jonathan Luisi
    University of Texas Medical Branch, Galveston, Texas, United States
    Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, United States
  • Giulio Taglialatela
    University of Texas Medical Branch, Galveston, Texas, United States
  • Gracie Vargas
    University of Texas Medical Branch, Galveston, Texas, United States
    Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, United States
  • Massoud Motamedi
    Ophthalmology, University of Texas Medical Branch, Galveston, Texas, United States
    Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, United States
  • Footnotes
    Commercial Relationships   Hossein Nazari Khanamiri, None; Mauro Montalbano, None; Jonathan Luisi, None; Giulio Taglialatela, None; Gracie Vargas, None; Massoud Motamedi, None
  • Footnotes
    Support  UT Brain Grant
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1882. doi:
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      Hossein Nazari Khanamiri, Mauro Montalbano, Jonathan Luisi, Giulio Taglialatela, Gracie Vargas, Massoud Motamedi; Age-dependent structural and microvascular changes in retina associated with progressive amyloid-β and Tau deposition in triple transgenic mouse model of Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1882.

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

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Abstract

Purpose : Diagnosis of early-stage Alzheimer’s disease (AD) is crucial for successful treatment of the disease. Retina, as an extension of the brain, shows pathologic changes in AD and is easily accessible for noninvasive imaging modalities. The aim of this study was to characterize spatiotemporal dynamics of neurovascular coupling and amyloid-β (Aβ) and Tau deposition in the retina in a model of AD exhibiting age-dependent progressive neuropathology including plaques and tangles. The model used in this study, 3xTg-AD, harbors three mutations of human APP (Swedish mutation), Tau (P301L mutation), and presenilin-1 genes and manifests pathologic changes that resemble those of human.

Methods : Morphological changes in the retina of 4-, 8-, 12-months old 3xTg-AD mice were quantified using Bioptigen system for optical coherence tomography (OCT) and angiography (OCTA). The animals were euthanized at each time point and retina flat mounts were immunostained for Aβ, Tau, ganglion cell (GC) marker TUJ-1, and collagen IV. Temporal and spatial deposition of Aβ and Tau in the retina, GC density, and vascular changes were correlated.

Results : Progressive thinning of the retina and the loss of retinal nerve fiber bundles, monitored by OCT, accompanied increased deposition of Aβ and Tau, decreased GC density, and changing GC morphology. The retinal nerve fiber layer thickness decreased by 25% as a function of aging (4-8 months). Aβ deposition was concentrated primarily in the inner aspect of ganglion cell layer (GCL) at the junction of GC and their axons whereas Tau deposition was localized predominately in nerve fiber layer. Furthermore, capillary wall exhibited increased Aβ localization and morphological abnormalities with age.

Conclusions : Age-dependent increase in Aβ and Tau deposition in GCL and retinal vessels correlates with progressive retinal thinning. Non-invasive monitoring of retinal morphology and vascular changes using OCT-based imaging techniques may provide new avenues for diagnosis and monitoring of AD progression.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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