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Permanent link (DOI): https://doi.org/10.7939/R3B37N

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Electrophysiological and Genetic Aspects of Age-Related Macular Degeneration (AMD): Treatment Implications Open Access

Descriptions

Other title
Subject/Keyword
pharmacogenetics
genetics
age-related macular degeneration
electrophysiology
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Dimopoulos, Ioannis
Supervisor and department
Sauvé, Yves (Ophthalmology and Physiology)
Examining committee member and department
Matthew, Tennant (Ophthalmology)
MacDonald, Ian (Ophthalmology)
Allison, Ted (Biological Sciences)
Department
Medical Sciences-Ophthalmology
Specialization

Date accepted
2014-07-10T09:54:38Z
Graduation date
2014-11
Degree
Master of Science
Degree level
Master's
Abstract
Age-related macular degeneration (AMD) is considered a heterogeneous group of disorders. Although many genes influence susceptibility to disease, none has shown to be the primary contributor. To identify genetic contributors, distinct AMD phenotypes need to be established. We relied on electrophysiological testing (ERG) to detect homogeneous subgroups for future genotype-phenotype association studies. We also classified AMD patients based on refractoriness to anti-VEGF treatment to investigate genetic associations with known high-risk single nucleotide polymorphisms (SNPs). Our results suggest that generalized cone dysfunction and delayed rod phototransduction activation characterizes a subset of AMD patients, while impaired dark adaptation constitutes a universal feature of the disease. We were unable to unify all patients unresponsive to anti- VEGF monotherapy under a single SNP haplotype, highlighting the genetic complexity underlying the disorder and its treatment prediction. By applying a novel approach to investigate potential pharmacogenetic interactions, we provided evidence that variation in multiple susceptibility loci may better explain differential response to anti-VEGF therapy. Treatment with prolonged VEGF blockade was found to result in inner retina dysfunction in a subset of AMD patients. Therefore, pharmacogenetic research holds promise in developing individualized approaches for AMD treatment in the future, which will not only optimize final patient outcome, but also reduce the risk of adverse effects.
Language
English
DOI
doi:10.7939/R3B37N
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Dimopoulos IS, Tennant M, Johnson A, Fisher S, Freund PR, Sauvé Y. Subjects with unilateral neovascular AMD have bilateral delays in rod-mediated phototransduction activation kinetics and in dark adaptation recovery. Invest Ophthalmol Vis Sci. 2013 Aug 5;54(8):5186-95.

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