Optometry and Vision Sciences - Theses
Permanent URI for this collection
Search Results
1 - 5 of 5
-
ItemNo Preview AvailableInvestigating Diagnostic and Drug Efficacy Retinal Biomarkers in Parkinson’s Disease( 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.
-
ItemSubcortical pathways for colour vision( 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)
-
ItemCharacteristics of tritanopia and other researches into defective colour vision( [1964])The so called "red-green" forms of defective colour vision are relatively common and have been actively studied since the end of the nineteenth century. Helmholtz (1909) and other German physiologists and physicists made the first precise colorimetric-investigations of human vision. Since this "German period" the study of colour vision was pursued principally by Anglo-saxon physicists and physiologists. In 1935, Pitt published his monograph Characteristics of Dichromatic Yision and W. D. Wright published his Researches on Normal and Defective Colour Vision in 1947. Both these publications continue to form a foundation for current research in defective colour vision. Whilst our knowledge of "red-green" defective colour vision became remarkably accurate and detailed the so called "Blue-yellow" defects were neglected. Wright (1947) refers briefly to tritahopia and tritanomaly commenting that "the amount of reliable information about tritanopia is meagre" (p297) and that "no tritanomalous observers have yet been discovered who could make tests at the colorimeter" (p320). The comparitive rarity of these blue-yellow colour vision defects was the principal reason for the neglect. Wright (1947) at the time suggested the incidences of tritanopia and tritanomaly were both one in a million but warned that these figures "are necessarily very approximate" (p303). However Schmidt (1943) had screened 21,000 visitors to an exhibition and found one case of tritanomaly. The rarity of these two defects is to some extent the product of the kind of screening tests employed. The Ishihara plates make no attempt to test for "blue-yellow" defects and the Nagel anomaloscope uses the Rayleigh equation. An attempt to modify the Nagel anomaloscope to provide a BG equation was not successful (Jaeger 1955). The Stilling pseudo-iso chromatic plates included some plates for the detection of blue-yellow defects, but the Ishihara suplanted this test in many countries. The identification of blue-yellow defects in mass and routine colour vision testing was made practicable by Farnsworth. Farnsworth (1943) produced his Farnsworth-Munsell 100 Hue test and has devised single pseudoisomatic plates which have been shown to be a very effective means of identifying this class of colour vision defect (Jaeger, 1955). One of these plates was used by Wright (1952) in a mass survey which yielded 17 confirmed cases of tritanopia. On the basis of this survey Wright calculated that the incidence of tritanopia was between 1 in 13,000 and 1 in 65,000, the higher freauency being the more likely. This is a much higher incidence than the 1 in 1,000,000 that had suggested previously, but much lower than the 2 in 100 of red-green dichromats among men.
-
ItemAn investigation of the blue-sensitive mechanisms of human colour vision( 1971)The characteristics of the blue-sensitive process of human colour vision have been explored by means of the two-colour increment threshold technique of W. S. Stiles and the measurement of retinal directional sensitivity. The objectives were a) to find points of difference between the three independent blue-sensitive mechanisms π1, π and π3 which might lead to reasonable hypotheses concerning their physiological basis and functional role, and b) to establish whether the unique threshold behaviour of the blue process at the fovea is due to an absence of blue cones as Wald (1967) has concluded. It has been found that the π3 mechanism has similar characteristics to π1; it is absent in tritanopia, exhibits extensive complete spatial summation and has high directional sensitivity. The π2 mechanism appears to be less directionally sensitive. Both π1 and π3 have been demonstrated at the central fixation area of the fovea. On the basis of these results and evidence in the literature a theory of the blue-sensitive mechanisms is proposed.
-
ItemSegregation within afferent pathways in primate vision( 2009)The current knowledge of the visual pathways in primates includes the patterns of projection from the retina through the dorsal lateral geniculate nucleus (dLGN) to the striate cortex (V1) and the extra-striate projections towards the dorsal and ventral streams. Cells with short wavelength sensitive cone (S-cone) inputs in the dLGN have been studied extensively in New World marmosets but not in Old World macaques. This thesis presents results from studies in the macaque monkey which are more relevant to humans since humans are closer in evolution to Old World than New World monkeys. The spatial, temporal, chromatic and orientation preferences of neurons in the dLGN of the macaque were investigated by electrophysiological methods. The physiological findings of cells with S-cone inputs were compared to cells with opponent inputs from the long and medium wavelength sensitive cones (L-cones & M-cones, respectively). The cells receiving S-cone inputs (blue-yellow or B-Y cells) preferred lower spatial frequencies than the cells with opponent L-cone and M-cone inputs (red-green or R-G cells). Orthodromic latencies from optic chiasm stimulation were measured where possible to distinguish differences in conduction velocity between the cell groups. Although the B-Y cells usually had longer latencies than R-G cells, there wasconsiderable overlap between the cell groups. The recorded cells were localised through histological reconstruction of dLGN sections stained for Nissl substance. The distribution of B-Y cells within the dLGN was compared to the distribution of R-G cells. The majority of B-Y cells were located within the intercalated koniocellular layers as well as the koniocellular bridges (extensions of the koniocellular layers into the adjacent parvocellular layers). The B-Y cells were also largely segregated within the middle dLGN layers (K3, P3, K4 & P4). The R-G cells were mainly concentrated within the parvocellular layers (P3, P4, P5 & P6) and were evenly distributed throughout the middle and outer layers of the dLGN. The study also included recordings from the extra-striate middle temporal area (MT) to determine whether a fast S-cone input exists from the dLGN to area MT which bypasses V1. The pattern of cone inputs to area MT neurons was investigated before and during inactivation of V1. The inactivation was done through reversible cooling with a Peltier thermocouple device or focal inactivation with y-amino butyric acid (GABA) iontophoresis. Precise inactivation of V1 to the topographically matching visual fields of the recording sites in area MT revealed a preservation of all three coneinputs in many cells. The subcortical sources of these preserved inputs are discussed with their relevance to blindsight, which is the limited retention of visual perception after V1 damage. Analysis of the latencies of area MT cells revealed a rough segregation into latencies faster or slower than 70 ms. Cells both with and without a significant change in response during V1 inactivation were present in each group. The findings reported in this thesis indicate that some of the preserved inputs in area MT during V1 inactivation may be carried by a direct input from the dLGN which bypasses V1.