Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biology

Supervisor

Dr Kathleen Hill

Abstract

The prevalence of aging-related retinal degenerative disorders is rising amongst human populations and the origins and early mechanisms of retinal disease remain poorly understood. A model of premature aging, the harlequin mouse, was used to test the hypothesis that parainflammation, a response to inflammation correlates with functional deficits preceding observed structural losses. In vivo retinal imaging showed thinning of the outer nuclear layer, the earliest retinal structural biomarker observable, while quantitative gene expression assays showed increases in mRNA levels of the Major Histocompatibility Complex-I, a marker of both increased inflammation and microglial activation. In situ immunohistochemistry showed greater numbers of activated resident microglial cells present in the harlequin versus wild type mouse retina at a young age. A parainflammatory response as an early disease mechanism opens the door to explore the efficacy of known anti-inflammatory therapies and better understand the link between aging and vision loss.

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