Optometry and Vision Sciences

Given the eye is an embryological outpouching of the brain, there is growing interest in the characterisation of retinal biomarkers in neurodegenerative disease to better facilitate timely diagnosis and treatment. Recent studies report a number of visual symptoms in people living with Parkinson's disease (PD), lending evidence to support the need to prioritise non-motor manifestations of PD, given that some precede the onset of motor decline by years if not decades. The retina offers a unique opportunity to directly visualise structural and functional changes in neurons that occur with PD pathogenesis. The development of non-invasive and relatively inexpensive retinal assessment modalities such as optical coherence tomography (OCT) and electroretinography (ERG) has enabled clinicians and researchers to assess these in vivo changes in people living with PD and in animal models of PD. However, the pathological mechanisms underlying visual and retinal dysfunction in PD remain incompletely understood. The overarching aim of this thesis was to explore and investigate retinal changes in function and structure that occur in people living with PD and a Parkinson’s disease rodent model, and to consider if such in vivo measures are sensitive to acute levodopa (L-DOPA) treatment. Using the A53T transgenic (Tg) mouse model of alpha-synuclein (a-syn) overexpression, we demonstrate that the accumulation of phosphorylated (pSer129) a-syn in outer retinal layers was correlated with cone photoreceptor dysfunction and degeneration. We speculate that this association between pSer129 a-syn and dysfunction may be related to an underlying pathophysiology. Moreover, we show that acute L-DOPA treatment can dynamically ameliorate retinal deficits in function in A53T Tg animals. As a proof of principle in translation, we evaluate changes in retinal function and structure in clinical Parkinson's disease, before and after single doses of L-DOPA following partial washout conditions. While no ameliorative effects were observed post L-DOPA treatment in this pilot study, PD participants had altered cone photoreceptor function and structure compared to age-matched controls, as indicated by poorer colour vision performance, reduced macular visual field sensitivity, and attenuated light-adapted a-wave and b-wave amplitudes. Overall, this body of work deepens our understanding of outer retinal changes in function and structure, driven in part by abnormal a-syn deposition, that occur in Parkinson's disease. Collectively, these findings provide further insight into dopamine and alpha-synuclein interactions in the retina as well as highlighting the utility of outer retinal measures as effective biomarkers for future application to Parkinson’s disease medical research and drug discovery.

This thesis shows that amyloid beta found in the brain is also present in the retina of a murine model of Alzheimer’s disease. By applying non-invasive retinal techniques, we show that neuronal structural and functional changes occur early in this model and that these are associated with vascular dysfunction. Such retinal hallmarks differentiate Alzheimer's changes from healthy ageing mice and provide evidence that the retina is a viable biomarker for dementia.

Ageing is a key risk factor for ocular diseases, though age-related changes in the eye have not been fully characterised. This study investigated age-related changes in retinal function, structure and their response to acute and chronic stress in Long Evans rats. With age, both retinal structure and function decline and the retina loses its ability to cope with acute stress. When exposed to mild chronic stress, older eyes suffered greater functional damage than younger eyes.

Optometry and Vision Sciences - Theses

Permanent URI for this collection

Filters

Date

Author

Subject

Type

Settings

Sort By

Results per page

Statistics

Citations

Search Results