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Eye Movement Desensitization Reprocessing (EMDR) therapy has burst upon the psychotherapeutic scene as a time-limited, cost-contained, and efficacious treatment for anxiety, stress, and psychological trauma. Although this therapy has been pronounced as revolutionary by its inventor, Francine Shapiro, it has distinct historical precedents. The explanatory models of pathogenic memory and dissociation theory, and the reliance on mechanical inference for objectivity make EMDR therapy familiar and salient. Notions of suggestion and hypnosis, and the eye-movement component of therapy are presented as discontinuous with clinical and theoretical practice, in order to free them from the tainting associations of pseudo-science and quackery. By connecting the current EMDR movement with the conceptual and practical history of traumatic memory, dissociation, and suggestion, I argue that EMDR is not revolutionary. It is a powerful technology of the self, normalizing and valourizing certain ways of behaving and thinking. Shapiro's implicit assumptions that psychological suffering is pathological, and that early traumatic events are indelibly encoded, stored and dissociated in the brain are problematized. A brief commentary on the moral, political, and psychotherapeutic implications of EMDR therapy is provided.

Idiopathic endogenous posterior uveitis encompasses a spectrum of chronic intraocular inflammatory disorders which are thought to be autoimmune in nature. The animal model experimental autoimmune uveoretinitis (EAU) is mediated by CD4+ T-lymphocytes, and has proved invaluable in the study of the underlying immunopathogenesis of uveitis and alternative immunosuppressive therapies, for example, oral tolerance induction. This thesis describes, in a model of retinal-extract induced EAU, the effects of intranasal administration of retinal antigens prior to induction of EAU with retinal extract. The thesis has demonstrated that immunisation with emulsified retinal extract and CFA (without pertussis) induces a dose-dependent intraocular inflammation, which at high doses leads ultimately to total loss of rod photoreceptor outer segments and retinal necrosis. A course of intranasal inoculations with retinal extract (tolerance induction), prior to immunisation with antigen suppresses the histological and clinical response of EAU. Animals which were tolerised with microgram quantities of antigen showed evidence of mild inflammation of the ciliary body and inner retinal vessels (vasculitis) but no evidence of direct photoreceptor damage when compared to controls. Intranasal inoculation with retinal extract suppressed S-Ag-induced EAU but not vice versa, despite the ability of S-Ag intranasal inoculations to suppress S-Ag induced disease. Tolerised animals demonstrated normal antibody responses to S-Ag, IRBP and retinal extract, and exhibited a significantly suppressed delayed hypersensitivity response to retinal extract but normal response to a non-specific antigen, PPD. Adoptive transfer of splenocytes from tolerised animals suppressed the induction of EAU in some naive recipients. These findings suggest that active suppressor mechanisms are involved in the induction of tolerance, which concurs with other findings of CD8+ T-lymphocyte mediated suppression in oral tolerance models. In order to study the future application of 'tolerance therapy', we attempted to suppress sensitised animals by intranasal tolerance which resulted in an incomplete suppression of EAU.

The effect hand action representations have on language processing was investigated using eye-tracking techniques. Subjects were shown an image of a hand action and asked to hold the action in working memory while reading a sentence, which described an actor lifting, or using an object. The displayed hand actions were related to either a functional (using) or volumetric (lifting) interaction with an object that matched or did not match the object mentioned in the sentence. A neutral condition was also used which displayed a black circle instead of a hand action. No significant difference was found between any of the five working memory conditions for gaze duration, probability of word skipping, and several other dependent measures utilized in the study. A significant difference was found for gaze duration when the conditions were restricted. Shorter gaze duration was observed for the hand action congruent to both the context and the object mentioned in the sentence and longer gaze duration was observed for the hand action congruent to only the sentence context. Some possible explanations of the results are that subjects may not have encoded the hand actions as action representations, or that hand actions represented in working memory have no effect on sentence processing. / Graduate / 0633

The effect hand action representations have on language processing was investigated using eye-tracking techniques. Subjects were shown an image of a hand action and asked to hold the action in working memory while reading a sentence, which described an actor lifting, or using an object. The displayed hand actions were related to either a functional (using) or volumetric (lifting) interaction with an object that matched or did not match the object mentioned in the sentence. A neutral condition was also used which displayed a black circle instead of a hand action. No significant difference was found between any of the five working memory conditions for gaze duration, probability of word skipping, and several other dependent measures utilized in the study. A significant difference was found for gaze duration when the conditions were restricted. Shorter gaze duration was observed for the hand action congruent to both the context and the object mentioned in the sentence and longer gaze duration was observed for the hand action congruent to only the sentence context. Some possible explanations of the results are that subjects may not have encoded the hand actions as action representations, or that hand actions represented in working memory have no effect on sentence processing. / Graduate / 0633

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The central purpose of this research has been to examine the possibility of the plasticity of individual saccadic parameters and to identify their patterns of covariation. Experiments using trial-by-trial feedback or continuous on-going feedback methods demonstrated that the saccadic generator can prolong the duration of a saccade above normal levels. However, slowed peak velocities were only evident with continuous feedback. The results showed that although continuous feedback was a more effective method for inducing modifications of saccade trajectories, the effects of trial-by-trial feedback schedules were enhanced by distributing the training over several days. The instructions to produce slow saccades caused a 'staircase' pattern of eye movements in which a continuous sequence of hypometric saccades was manifested. These saccades had latencies 400-600 msecs longer than normal visually controlled eye movements. Detailed measurements (chapter 4) of the latencies of the saccadic components indicated that each component was programmed independently. In chapter 5 the Gurevich claim that a saccade velocity depends only on the spatial magnitude of the saccade was tested by measuring saccades of equivalent amplitudes to targets which varied in movement duration and velocity. The accuracy of saccades but not their peak velocities or durations was sensitive to manipulations in the temporal characteristics of the target. Experiments in chapter 6 showed that the use of spatial signals in the aiming of a saccade can be systematically controlled. When subjects were trained for several days in a visual discrimination task the accuracy of the initial saccadic movement increased over time. The results of these experiments seriously question the Young and Stark (1963b) ballistic model and other formulations (Westheimer, 1954b, 1973; Yarbus, 1967) which assume that the saccadic system operates according to stereotyped mechanisms.

This work introduces novel approaches to enhance targeting of pharmacotherapies to cornea, ciliary body, choroid, and posterior segment of the eye using microneedles as a drug delivery platform. The first part of the work determines the ability to deliver protein therapeutics into the cornea using coated microneedles to suppress corneal neovascularization in a rabbit model. The data show that highly targeted delivery of the anti-vascular endothelial growth factor protein therapeutic gave a better biological response of suppressing neovascularization with 11,900 times less dosage compared to topical administration. The second part of the research aims to develop novel formulations to target ciliary body and choroid via suprachoroidal delivery. The results show that a strongly non-Newtonian fluid can be used to slow down the spreading of the particles at the injection site up to 2 months. The results also show that a high molecular weight formulation with weakly non-Newtonian fluid can be used to reach 100% coverage of the choroidal surface with a single injection. The third part of the research aims to determine the biological response of targeting anti-glaucoma therapeutics to the ciliary body in a rabbit model. The results show we can achieve 500- to 1000-fold dose sparing by targeted delivery via supraciliary delivery. The fourth and last part of the research aims to develop novel emulsion droplets to target different locations within the eye using a gravity-mediated delivery technique via suprachoroidal space injection. The results show that we can deliver up to 73% of injected polymeric particles posterior to the equator of the eye. Overall this work demonstrates that microneedles have the capability to deliver pharmacotherapies to cornea, ciliary body, choroid, and posterior of the eye in a highly targeted manner and provide significant dose sparing in the rabbit model.

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