Advisory Committee Chair
Advisory Committee Members
Lori L McMahon
Thomas Van Groen
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Optometry
Alzheimer’s disease (AD) is a debilitating, and the most prevalent, type of dementia that is manifested by cognitive deficits, anomalous protein metabolism, cell loss, and pathological alterations in several neurotransmitter systems, particularly the cholinergic and glutamatergic systems. Moreover, AD is associated with visual deficits that have been reported to occur even in the early stages of the disease and may precede conspicuous cognitive impairment. To date, the underlying causes of the visual deficits and whether they stem from retinal or cortical abnormalities remain poorly understood. The following studies aimed at establishing whether the pathological changes observed in the cerebrum are also present in the retina and assessing AD’s influence in retina’s physiological responses. We used quantitative polymerase chain reaction and immunohistochemistry to assess changes in acetylcholine receptor (AChR) gene expression, gliosis, retinal cell number in the Tg-SwDI mouse model as compared to age-matched wild-type (WT). Young adults and middle-aged adults Tg-SwDI mice exhibited initial upregulation of AChR gene expression, but downregulation in old adults. Furthermore, young adult transgenic mice displayed significant cell loss in the inner retina and photoreceptor layer. Middle-aged adult and old adult mutants exhibited increased astrocytic gliosis and cholinergic cell loss. Electroretinography (ERG) was employed to measure the amplitude and implicit time of retinal responses from TgF344-AD rat model and age-matched WT at 9 and 16 months of age. 9-month mutants exhibited higher responses from several retinal cells, but lower responses from off bipolar cells and Müller cells. 16-month TgF344-AD rats displayed lower scotopic critical flicker fusion threshold and photoreceptor responses, and slower implicit time for on bipolar cell responses, at several light intensities. These data collectively indicate that AD-related changes observed in the cerebrum are also present in the retina and may be, at least in part, responsible for the visual deficits associated with the disease. Furthermore, we demonstrated that AD pathology affects retinal cells’ physiological responses and that ERG can be employed as a suitable means to detect AD-related visual changes to ultimately serve as an efficacious diagnostic tool to identify the disease in its earlier stages, thus improving treatment efficacy.
Souza, Fred, "The Eye As A Window To The Alzheimer’S Disease Brain" (2017). All ETDs from UAB. 3014.