Optometry and Vision Sciences - Theses
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ItemNo Preview AvailableFunctional and structural adaptations to ageing and acute intraocular pressure elevation in mouse retina( 2021)In response to stress, neurons undergo a series of adaptations, which include changes to their synapses, dendrites and eventually axons and cell bodies. One might presume that such stress responses help to prevent cell death, providing a window of time where recovery remains possible. As glaucoma is a disease of the ageing, it may be reasonable to suggest that older eyes somehow show poorer adaptations to stress or have reduced intrinsic abilities to detect pressure changes in their environment (e.g., via mechanosensitive channels such as transient receptor potential (TRP) channels), and thus less capacity to recover. Whilst support for these ideas can be gleaned from a range of studies in other systems including the central nervous system, there has been less work in this area in the context of glaucoma. The overarching aim of the thesis is to understand the functional and structural adaptations that occur in normal ageing, and to consider if such age-related changes modify the way that retinal ganglion cells (RGCs) cope with intraocular pressure (IOP) elevation. Using the mouse as a platform, it was possible to show that in normal ageing, there was a relative preservation of ganglion cell function despite an age-related decline in outer retinal responses. Age-related inner retinal functional adaptations were associated with increases in bipolar cell sensitivity to light and changes to RGC dendritic complexity. Ageing was also associated with slower recovery from a short period of controlled IOP elevation. IOP elevation resulted in smaller ON RGCs in both young and older mice. Importantly, analysis of RGC morphology showed that better functional recovery in younger eyes was associated with adaptations in OFF RGC dendrites, which was not observed in older eyes. The absence of RGC morphological adaptations following IOP elevation may account for the delayed recovery in older eyes. Furthermore, better ganglion cell functional recovery in younger eyes was also associated with TRPV4 upregulation in the ganglion cell layer. In contrast, there was TRPV4 downregulation in older eyes. Consistent with the importance of TRPV4 upregulation for recovery, inhibiting TRPV4 further worsened recovery in older eyes. This work advances our understanding of age-related functional and structural adaptations, providing insights into how normal function is maintained in ageing, with potential negative impacts on the capacity for RGCs to recover from IOP elevation.
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ItemThe effects of ageing on ocular surface integrity( 2019)Purpose: Ageing is recognised as a major risk factor for several ocular pathologies, including dry eye disease. The aim of this thesis was to characterise the specific effect of ageing on key ocular surface parameters, in humans and mice. We hypothesised that there would be common ageing effects in both species that paralleled the pathophysiological features observed in dry eye disease. Method: The animal study involved healthy C57BL/6 female mice, aged 2 months (young, n=10) and 22 months (aged, n=10). Clinical assessments included measurements of corneal sensitivity (Cochet-Bonnet aesthesiometry, which is a contact corneal aesthesiometer), tear secretion (Phenol red thread test), tear film osmolarity (TearLab osmometer) and corneal thickness (optical coherence tomography). The anatomical integrity of the corneal nerves was examined ex vivo (using immunohistochemistry) by quantifying nerve density in the superficial epithelium (superficial terminals) and sub-basal plexus. The density and tree area of resident epithelial dendritic cells (DCs) were assessed using immunofluorescence and confocal microscopy. For the clinical study, 37 healthy male and female participants (15 male participants and 22 female participants) were recruited, and divided into four age categories: 20-35 years, 36-50 years, 51-65 years, and >65 years. Participants underwent a comprehensive characterisation of ocular surface health, including quantification of tear osmolarity, blink rate, slit lamp biomicroscopy and corneal sensitivity (using non-contact corneal aesthesiometry). In vivo confocal microscopy (IVCM) was performed to quantify a range of corneal nerve parameters, microneuroma density and DC density, in the central and peripheral cornea. Results: In the animal study, aged mice had significantly higher tear secretion, lower corneal sensitivity and a thicker corneal stroma but thinner epithelium compared with young mice. There was no significant inter-group difference for tear osmolarity. Aged mice showed a significantly lower cornea nerve density, in both the superficial terminals and sub-basal plexus, relative to young mice. DC density and morphology were similar in both age groups. In the human study, older age was associated with a reduction in central corneal sensitivity to a room temperature air stimulus, but not to a cold temperature stimulus. Tear osmolarity remained within normative ranges (<308mOsmol/L) in all age groups, although it was relatively higher in this parameter amongst individuals aged 36 to 50 years, compared to the 20 to 35 year olds (p = 0.0047). A range of ocular surface parameters, including corneal sub-basal nerve plexus density, DC density and microneuroma density were not subject to ageing effects but showed eccentricity-dependent differences. Blink rate and most standard clinical biomicroscopic findings were not significantly different between age groups. Conclusion: Ageing has differential effects on ocular surface parameters. A reduction in corneal sensitivity, and a relative maintenance of corneal DC density, was evident in older eyes in both species. The apparently disparate findings in relation to corneal nerve density between mice and humans may relate to the established limitations of in vivo imaging techniques, particularly with respect to image resolution. These findings, relating to ocular surface changes with physiological ageing, are of value for understanding the potential contribution of the ageing process to ocular surface diseases.
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ItemPerceptual suppression mechanisms in healthy ageing( 2017)Healthy ageing alters contextual spatial interactions such as centre surround contrast suppression and spatial suppression of motion discrimination. However, the exact neural mechanisms that underlie age related changes to contextual spatial interactions are still elusive. The body of work reported in this thesis explored the perceptual mechanisms behind altered contextual spatial interactions in younger and older adults using psychophysical and neuroimaging methods. Experiment 1 investigated the strength of foveal centre surround contrast suppression under intraocular and interocular viewing for two stimulus durations (40 ms and 200 ms) in younger and older adults. Foveal intraocular center surround contrast suppression decreased with longer stimulus duration whereas interocular surround suppression did not, suggesting contributions from separate mechanisms to these forms of suppression. In addition, intraocular center surround contrast suppression was increased in older adults compared to younger adults; however, interocular suppression was similar in both groups. Experiment 2 studied the effect of orientation of the surround grating in relation to the orientation of the centre grating (surround orientation effect) on centre surround contrast suppression under intraocular and interocular viewing in younger and older adults. Interocular and intraocular centre surround contrast suppression showed different surround orientation effect, and older adults demonstrated unaltered levels of surround orientation effect compared to younger adults under both intraocular and interocular viewing. Experiment 3 measured Gamma Aminobutyric Acid (GABA, the principal inhibitory neurotransmitter of the adult brain) levels in visual cortex of younger and older adults using magnetic resonance spectroscopy. Visual cortical GABA levels were increased in older adults compared to younger adults. In addition, visual cortical Glx (combined estimate of glutamate - the principal excitatory neurotransmitter, and glutamine) levels were reduced in older adults compared to younger adults. Neither GABA levels nor Glx levels in visual cortex correlated with foveal centre surround contrast suppression. The final experiment of this thesis (Experiment 4) investigated the relationship between visual cortical GABA levels and performance on two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion discrimination and binocular rivalry. Both younger and adults participated in this experiment as well. Increased visual cortical GABA levels were associated with prolonged binocular rivalry percept durations and reduced spatial suppression of motion discrimination. The experimental frameworks used in the thesis were based on our modern understanding of cortical circuits that are implicated in mediating centre surround contrast suppression, and a neuroimaging technique that could potentially link physiology with behaviour. The novel findings reported in thesis answered some of the important questions related to perceptual surround suppression in younger and older adults. The current findings suggested that healthy ageing differentially affects distinct forms of suppression arising at various levels of the visual pathway, and challenged prior assumptions regarding age related changes to GABA levels within the visual cortex and its association with centre surround contrast suppression and spatial suppression of motion discrimination.
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ItemAge-related changes in structure, function and response to stress in the rat retina( 2016)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.
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ItemAudiovisual synchrony perception in older adults( 2015)The purpose of this project was to examine differences in the behavioural and neural measures of audiovisual synchrony perception between younger and older adults. To accurately perceive events in the natural scene, the human perceptual system needs to combine related and segregate unrelated auditory and visual stimuli. The amount of temporal asynchrony is one of the key properties that define whether an auditory and a visual stimulus are related, and whether they should be perceived as originating from the same event. As older adults experience reduced visual contrast and hearing sensitivities, this project investigated audiovisual synchrony perception in older adults after scaling stimulus levels to individual detection thresholds. It was also investigated if older adults are able to realign their perception of audiovisual synchrony after adapting to asynchrony - an ability that is potentially important for correctly perceiving audiovisual pairs across distance. Additionally, this project investigated the impact of older age on the underlying neural time course for audiovisual synchrony perception. The results from this project demonstrated that older adults were less sensitive to audiovisual asynchrony even after scaling the stimuli to their own detection thresholds for visual contrast and sound intensity. Older adults also adapted less to sound-lag asynchrony adaptation as compared to the younger adults. In addition, older adults showed additional neural activity in the frontal and parietal regions in order to form perceptual decisions for audiovisual synchrony. The findings from this project could imply that older adults find it more difficult to correctly perceive related audiovisual events in a natural scene, particularly for distant events. The additional involvement of the frontal and parietal areas in older adults may indicate that they may compensate by recruiting extra neural resources to perform the same perceptual task as younger observers. This project also considered some future work that are required to understand the real-life implications of older age on audiovisual synchrony perception like the effect of spatial clutter (i.e. in crowds) and the effect of rapid adaptation. As a whole, the findings from this project added knowledge to the body of work of ageing on audiovisual synchrony perception.
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ItemContrast processing in ageing and early glaucoma( 2014)A natural visual experience commonly requires an ability to differentiate objects of supra-threshold contrast (contrast discrimination) and to adjust to changes in contrast (contrast adaptation). While the loss of contrast sensitivity with glaucoma has been well documented in the literature, the effect of glaucoma on supra-threshold contrast processing is less studied. This thesis investigated the effects of early glaucoma on contrast discrimination and rapid contrast adaptation. Additionally, alterations in retinal and cortical responses to supra-threshold contrast stimuli with glaucoma were investigated using electrophysiology techniques. As age is a risk factor for glaucoma, this thesis also considered the effects of normal ageing on contrast processing. The results of this thesis suggest that glaucoma can result in supra-threshold contrast deficits, with patients having early glaucoma demonstrating a reduction in rapid contrast adaptation and poorer contrast discrimination. As ageing did not alter rapid contrast adaptation, the assessment of contrast adaptation might be a useful functional tool in early glaucoma, although further studies are required to develop this. Further studies are also required to consider the implications of supra-threshold contrast deficits with glaucoma on natural vision. The smaller cortical deficits relative to retinal deficits revealed with electrophysiological recordings suggest that post-retinal abnormalities are minimal in patients with early glaucoma. Hence, there is a possibility that the supra-threshold contrast deficits seen in early glaucoma in this thesis may mainly arise from retinal abnormalities. There is also the possibility that post-retinal compensation resulted in minimal cortical deficits in patients with early glaucoma. Further experiments involving patients with more advanced glaucoma may help to elucidate post-retinal contrast processing mechanisms with glaucoma. In older adults, elevated cortical responses in the presence of reduced retinal responses suggest the possibility of age-related reduction in cortical inhibition. Altogether, the results of this thesis provide further understanding of the mechanisms underlying supra-threshold contrast deficits in early glaucoma and ageing.
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ItemPerceptual centre-surround processing in older adults( 2012)The aim of this thesis was to investigate the effects of perceptual centre-surround suppression in older adults. It has previously been shown that older adults show increased contrast-contrast surround suppression for textured centre-surround stimuli. As the amount of centre-surround suppression is known to depend on stimulus parameters such as contrast, orientation and size, the purpose of the current experiments was to use a variety of stimulus parameters in order to assess under which conditions older observers demonstrate increased surround suppression compared to younger adults. Two groups of adult observers one young and one old participated in centre-surround contrast matching tasks. Experiment 1 aimed to investigate border cues between centre and surround stimuli. Surround suppression was measured when centre and surround were presented in-phase and when they were presented out-of-phase. Older observers produced greater amounts of suppression for both conditions when compared to younger observers indicating that the phase information at the border is not responsible for the increases in surround suppression. Additionally, Experiment 1 revealed that increases in surround suppression cannot be attributed to decreased contrast sensitivity of the older groups. Experiment 2 aimed to investigate surround suppression in older observers for drifting stimuli. Observers performed the contrast-contrast task as well as a motion discrimination task which has also been used to measure perceptual centre-surround suppression. Consistent with Experiment 1, older observers showed increased surround suppression for the contrast-contrast task, however performed similarly to younger observers for the motion discrimination task implying that the two tasks involve different mechanisms. Finally, Experiment 3 investigated the contrast ratios between the centre and surround. Results revealed that older adults showed increased surround suppression when contrasts were low, more specifically when centre contrast was low. When centre-surround contrasts were high (80/80%), younger and older observers performed similarly. The findings of this thesis demonstrate that perceptual contrast surround suppression is strengthened in older adults when compared to younger observers for a variety of stimulus conditions. The findings of Experiment 3 provide a possible explanation for the differences found between analogous perceptual tasks (contrast vs. motion tasks), with results enabling some inferences regarding neurophysiological mechanisms responsible for the age-related differences. Additionally, the results presented herein suggest that a series of perceptual tasks are needed in order to measure the balance of excitation and inhibition within the human visual system.
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ItemThe effects of ageing and visual field loss on visuomotor control( 2012)Aspects of visual localisation, such as foveal hyperacuity, decline with age. However, the effect of ageing on the visual localisation judgements required for goal-directed reaching movements has not been studied. It is also unknown whether pointing precision to such visual stimuli are altered with ageing. Further, the effects of visual impairment on these tasks are not understood. This thesis aimed to investigate the effects of ageing and compromised peripheral visual function on visual localisation and pointing precision. The first part of this thesis aimed to investigate the effects of ageing on visual localisation and pointing precision (Chapter 4). Experiment 1 consisted of a cohort of younger and older observers performing visual localisation and pointing tasks. The results suggest that both the visual localisation and pointing systems remain largely intact with ageing. However, the visual localisation precision of older adults was more affected by the removal of visual references than younger observers. These findings are encouraging for older adults; especially with the increasingly active part they play in the workforce, and society at large. In order to further probe the state of the older visuomotor system, the second part of this thesis investigated the pointing and visual localisation precision of older observers with compromised visual status (Chapter 5). Older adults with glaucoma, a chronic eye disease that results in reduced visual field sensitivity, were used as the model for compromised visual status in Experiment 2. Results suggest that patients with glaucoma show a reduced ability to locate objects both visually and manually. However, perimetry – a clinical measure of visual field sensitivity – provides only a small indication of the degree of this difficulty. Observers with glaucoma also showed a reduced benefit of binocularity compared with their older controls for visual localisation tasks, suggesting that reduced visual field sensitivity may inhibit aspects of binocular processing.