Apart from motor and sensory function loss, an injury to the spinal cord can cause sympathetic dysfunction, which has been shown to affect immune responses. In this thesis, data from five experimental studies have been collected to compare physiological and psychophysiological exercise responses between wheelchair athlete subgroups with different disabilities (tetraplegic, paraplegic, and non-spinal cord-injured). In two preparatory studies, physiological exercise responses to exhaustive (Chapter 4) and submaximal exercise (Chapter 5) were investigated in all three disability subgroups. Whilst reliability measures for peak oxygen uptake (VO2peak) were in a range observed previously in able-bodied athletes, the variation in tetraplegic athletes was larger when expressed relative to their VO2peak, questioning the use of this variable to track small changes in aerobic capacity in athletic populations. Submaximal physiological and psychophysiological exercise responses were found to be similar between disability subgroups when expressed as a percentage of VO2peak, justifying the protocol used in the laboratory study on mucosal immune function, which was based on the same percentages of VO2peak for all disability subgroups. The most extensive study of this thesis, detailed in Chapter 6, showed that single laboratory-controlled 60-min exercise sessions increase both salivary secretory immunoglobulin A (sIgA), a marker of mucosal immunity, and α-amylase, a marker of sympathetic activation in all three disability subgroups. However, the impaired sympathetic nervous system in tetraplegic athletes seemed to influence the fine-tuning of their sIgA response when compared with paraplegic and non-spinal cord-injured athletes, resulting in a larger exercise-induced increase of sIgA secretion rate when compared to paraplegic and non-spinal cord-injured athletes. Based on these results, the study detailed in Chapter 7 investigated sIgA responses in tetraplegic athletes during wheelchair rugby court training. Despite their disability, these athletes showed responses thought to be governed by the sympathetic nervous system, such as reductions of saliva flow rate as a result of strenuous exercise. Similarly, the responses observed in Chapter 8 imply a comparable trend of chronic sIgA exercise responses in tetraplegic athletes as found in the able-bodied population, namely a decrease in sIgA secretion rate during periods of heavy training. These are the first studies in wheelchair athlete populations to investigate mucosal immune responses. Interestingly, despite the disruption of their sympathetic nervous system, some responses in tetraplegic athletes are comparable with findings in able-bodied populations. It is possible that due to their highly trained nature, these tetraplegic individuals are able to compensate for their loss of central sympathetic innervation. This may be by way of adapted spinal reflex or parasympathetic nervous system activity, or increased sensitivity of receptors involved in autonomic pathways. Therefore, sympathetic nervous function in tetraplegic athletes may be qualitatively altered, but in parts still be functional.

While prolonged nearwork is considered to be an environmental risk factor associated with myopia development, an underlying genetic susceptibility to nearwork-induced accommodative adaptation may be one possible mechanism for human myopia development. As the control of accommodation by the autonomic system may be one such genetically predetermined system, this research sought to investigate whether an anomaly of the autonomic control of accommodation may be responsible for myopia development and progression. The emphasis of this work was determining the effect of altering the sympathetic input to the ciliary muscle on accommodation responses such as tonic accommodation and nearwork-induced accommodative adaptation in myopes and non-myopes. The first study of the thesis was based on observations of Gilmartin and Winfield (1995) which suggested that a deficit in the sympathetic inputs to the ciliary muscle may be associated with a propensity for myopia development. The effect of ß-antagonism with timolol application on accommodation characteristics was studied in different refractive error groups. Our results support the previous findings that a deficit of sympathetic facility during nearwork was not a feature of late-onset myopia. However it was found that classifying myopes according to stability of their myopia and their ethnic background was important and this allowed differentiation between accommodation responses and characteristics of the ciliary muscle autonomic inputs, with the greatest difference observed between Caucasian stable myopes and Asian progressing myopes. Progressing myopes, particularly those with an Asian background, demonstrated enhanced susceptibility to nearwork-induced accommodative adaptation and this was suggested to result from a possible parasympathetic dominance and a relative sympathetic deficit to the ciliary muscle. In contrast, stable myopes, particularly those with an Asian background, demonstrated minimal accommodation changes following nearwork (counter-adaptation in some cases), and increased accommodative adaptation with ß-antagonism, suggesting sympathetic dominance as the possible autonomic accommodation control profile. As ethnic background was found to be an important factor, a similar study was also conducted in a group of Hong Kong Chinese children to investigate if enhanced susceptibility to nearwork-induced changes in accommodation may explain in part the high prevalence of myopia in Hong Kong. Despite some minor differences in methodology between the two studies, the Hong Kong stable myopic children demonstrated counter-adaptive changes and greater accommodative adaptation with timolol, findings that were consistent with those of the adult Asian stable myopes. Both Asian progressing myopic children and adults also showed greater accommodative adaptation than the stable myopes and similar response profiles following ß-adrenergic antagonism. Thus a combination of genetically predetermined accommodation profiles that confer high susceptibility and extreme environmental pressures is a likely explanation for the increase in myopia over the past decades in Asian countries. The hypothesis that a sympathetic deficit is linked to myopia was also investigated by comparing the effect of â-stimulation with salbutamol, a ß-agonist, on accommodation with that of ß-antagonism using timolol. It was hypothesized that salbutamol would have the opposite effect of timolol, and that it would have a greater effect on subjects who demonstrated greater accommodative adaptation effects, i.e. the progressing myopes, compared to those who showed minimal changes in accommodation following nearwork. Consistent with the hypothesis, the effect of sympathetic stimulation with salbutamol application was only evident in the progressing myopes whom we hypothesized may have a parasympathetic dominance and a relative sympathetic deficit type of autonomic imbalance while it did not further enhance the rapid accommodative regression profile demonstrated by the stable myopes. Characteristics of the convergence system and the interaction between accommodation and convergence were also investigated in the Hong Kong children. No significant differences in response AC/A ratios between the emmetropic, stable and progressing myopic children were found and it was concluded that elevated AC/A ratios were not associated with higher myopic progression rate in this sample of Hong Kong children. However, ß-adrenergic antagonism with timolol application produced a greater effect on accommodative convergence (AC) in stable myopic children who presumably have a more adequate, robust sympathetic input to the ciliary muscle, but had little effect on AC of progressing myopic children. This finding again points to the possibility that the autonomic control of the accommodation and convergence systems may be different between stable and progressing myopia. The primary contribution of this study to the understanding of myopia development is that differences in the autonomic control of the ciliary muscle may be responsible for producing anomalous accommodation responses. This could have significant impact on retinal image quality and thus results in myopia development. This knowledge may be incorporated into computer models of accommodation and myopia development and provides scope for further investigation of the therapeutic benefits of autonomic agents for myopia control.