Optometry and Vision Sciences - Theses

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Subject: retina × Subject: colour vision × Type: PhD thesis ×

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    Investigating Diagnostic and Drug Efficacy Retinal Biomarkers in Parkinson’s Disease
    Tran, Katie Khanh Ngoc ( 2023-08)
    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.
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    Subcortical pathways for colour vision
    Szmajda, Brett A. ( 2006-09)
    Visual sub-modalities, such as colour, form and motion perception, are analysed in parallel by three visual “pathways” – the parvocellular (PC), magnocellular (MC) and koniocellular (KC) pathways. This thesis aims to further elucidate some properties of the subcortical pathways for colour vision. The experimental animal used throughout is a New World monkey, the common marmoset Callithrix jacchus. (For complete abstract open document)