Optometry and Vision Sciences - Theses
Permanent URI for this collection
Search Results
1 - 3 of 3
-
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.
-
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.
-
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.