Characterizing ocular pathology in an animal model of Alzheimer’s disease
department or school: Science, Faculty of
department or school: Microbiology and Immunology, Department of
data provider: DSpace
degree campus: UBCV
creator: Baeva, Maria-Elizabeth
issued: 2021-04-21T19:39:04Z
issued: 2021
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Previous studies have characterized common pathological hallmarks of Alzheimer’s disease such as amyloid accumulation and plaque consolidation in the brain. The difficulty in accessing the brain in vivo has remained a barrier to the diagnosis or measuring the progression of the disease. Studies have shown that, in addition to amyloid deposition, angiogenesis and increased blood-brain barrier permeability are present in the brain of Alzheimer’s patients and animal models. Our study investigated whether these pathologies could be recapitulated in a more accessible organ associated with the central nervous system: the eyes. Using the Tg2576 model of Alzheimer’s disease, a transgenic mouse model which expresses human amyloid, an increase in amyloid was seen in the eyes of these mice and it was determined that the amyloid coalesced primarily around retinal blood vessels. This link between amyloid and ocular vasculature prompted a pilot study using a proteome profiler and found increased proangiogenic factors in the eyes and brains of the Tg2576 mouse, 20 proteins of which were upregulated in both organs. Performing further analyses of functional pathways on these findings revealed several reoccurring proteins in several pathways across both organs, including chemokines and fibroblast growth factors. Additional evidence of angiogenic processes was determined via the increased expression of CD105, a marker of neoangiogenesis, in whole eye homogenates of Tg2576 mice. When the distribution of the increased vasculature was examined, while the Tg2576 retina did not have increased amounts of CD105⁺CD31⁺ microvessels, the choroid did have more CD31⁺ vessels. Importantly, expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin was decreased in the Tg2576 retinal pigment epithelia and in whole eye homogenates, respectively. Along with evidence of an increased presence of albumin in whole eye homogenates, these results suggest that there is increased permeabili…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/77857
note: CHARACTERIZING OCULAR PATHOLOGY IN AN ANIMAL MODEL OF ALZHEIMER’S DISEASE by Maria-Elizabeth Baeva B.Sc., The University of British Columbia, 2018 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Microbiology and Immunology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2021 © Maria-Elizabeth Baeva, 2021 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis entitled: Characterizing ocular pathology in an animal model of Alzheimer’s disease. submitted by Maria-Elizabeth Baeva in partial fulfillment of the requirements for the degree of Master of Science in Microbiology and Immunology Examining Committee: Dr. Wilfred A. Jefferies, Professor, Microbiology & Immunology, UBC Supervisor Dr. Jacqueline Quandt, Professor, Pathology, UBC Supervisory Committee Member Dr. Santa Ono, Professor, Ophthalmology and Visual Sciences, UBC Supervisory Committee Member Dr. Marc Horwitz, Professor, Microbiology & Immunology, UBC Additional Examiner iii Abstract Previous studies have characterized common pathological hallmarks of Alzheimer’s disease such as amyloid accumulation and plaque consolidation in the brain. The difficulty in accessing the brain in vivo has remained a barrier to the diagnosis or measuring the progression of the disease. Studies have shown that, in addition to amyloid deposition, angiogenesis and increased blood-brain barrier permeability are present in the brain of Alzheimer’s patients and animal models. Our study investigated whether these pathologies could be recapitulated in a more accessible organ associated with the central nervous system: the eyes. Using the Tg2576 model of Alzheimer’s disease, a transgenic mouse model which expresses human amyloid, an increase in amyloid was seen in the eyes of these mice and it was determined that the amyloid coalesced pr…
has type: Thesis/Dissertation
date issued: 2021-05
is shown at: 10.14288/1.0396871
language: eng
degree discipline: Microbiology and Immunology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/77857