No description available.

Experimental Autoimmune Uveoretinitis (EAU), is a T cell mediated disease used as a model for several human inflammatory conditions affecting the posterior segment of the eye, which are immune mediated or autoimmune in nature. In this study an improved method of Interphotoreceptor Retinol Binding Protein (IRBP) preparation was devised (liquid chromatography), in order to establish the poorly characterised Lewis rat model of IRBP induced EAU. The progress of ocular inflammation induced by IRBP was investigated, both histologically (resin embedded, H &'38 E stained) and immunohistologically with particular reference to cells of the mononuclear phagocyte system. CD4&'43 lymphocytes out numbered CD8&43 lymphocytes in early focal lesions of the uvea and sites of retinal perivascular and ciliary body infiltration. A dominance reversed during disease resolution. Macrophages were also prominent throughout EAU: ED2 tissue macrophages in early retinal lesions; a prolonged presence of CD11b/CD18 mononuclear cells in the choroid and retina and early 'mass migration' into the photoreceptor region; and ED3 inflammatory macrophages in the vitreous and photoreceptor region during the late phase of disease. Once characterised this model of EAU was manipulated in vivo by the immunosuppressant macrolides Cyclosporin A, FK-506 and Rapamycin. In order to elucidate the key initiatory mechanisms responsible for the disease state the effects of immunosuppression on antibody production and in vitro cellular responses to antigen/mitogen were investigated.

This thesis considers two distinct but related topics concerned with the analysis of images of the ophthalmic fundus. The first involved the differentiation of automatically detected retinal microaneurysms from other spurious objects. A review of the current literature indicated that there had been no rigorous comparison of automated methods of classification for this type of ophthalmological task. Three classification techniques were investigated; a rule based system, linear discriminant analysis and a learning vector quantizer artificial neural network. Each classifier was trained and tested on the same pair of datasets, and the results analysed using receiver operating characteristic curves. It was found for this application that the rule based system performed marginally better than the linear discriminant analysis approach and both were superior to the neural network method. Whilst the improved performance of the rule based system may, in this clinical diagnostic situation, justify its higher development effort, the simplicity and transparency of the statistical method had much to commend it. The second investigation explored methods of completely segmenting the retinal vessel structure from the fundus image. Although a number of studies have considered different parts of the problem, few integrated solutions have been proposed. Each of the steps required were identified and analysed with the objective of integrating them into a fully automated segmentation and analysis system. Some of the problems were successfully resolved but others were either not completely resolved or were shown to be intractable given the current visual description of the problem.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

The Notch signalling pathway is a highly conserved cell-to-cell signalling pathway involved in developmental cell fate determination in all metazons. When Notch is signalling, differentiation is inhibited and a progenitor-like state is favoured. This signalling pathway has been implicated in the developing retina, where the inhibition of Notch has been shown to skew the proportion of different retinal neuronal cell types. Although functional knockout studies have allowed us to characterize some of the roles of Notch in the retina, low protein levels have made it difficult to characterize the location of Notch receptors and ligands in neuronal tissue. Here we sought to characterize the localization of the Notch signalling pathway components in both the developing and the adult mouse retina. Using RT-PCR we were able to show the presence of mRNA for Notch receptors, ligands, and DNA binding cofactors for the Notch intracellular domain, CBF1, throughout postnatal development as well as in the adult retina. In situ hybridization confirmed the presence of Notch1, Notch2, and CBF1 mRNA in the embryonic (E14.5) and early postnatal (P1.5) retina similar to what has been reported in earlier studies, but in the adult retina (P40), levels were below detection. To further explore the role of Notch in the adult retina we used two transgenic mouse reporter models in which a Notch responsive element directs the expression of EGFP or Venus. In the adult retina of the NTR line (Tg(Cp-EGFP)25Gaia/J) reporter expression was detected in rod ON and cone type 2 OFF bipolar cells, as well as in a subset of both amacrine and ganglion cells. In the CBFRE:H2B-Venus line adult reporter expression was detected in photoreceptors, and a large proportion of both amacrine and ganglion cells. Together this data supports the conclusion that Notch is expressed and actively signalling in the retina throughout development and possibly in the adult retina, although below levels of in situ hybridization detection. These results represent the possibility of a previously unknown role for Notch in the adult retina. / Graduate / 0317

Thesis (M. Sc.)--University of Adelaide, Dept. of Anatomy and Histology, 1986. / Includes bibliographical references (leaves 259-265).

Thesis (M.S.)--University of Wisconsin--Madison, 1984. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 49-53).

Proefschrift--Utrecht. / Bibliography: p. 91-98.

Thesis (doctoral)--Utrecht, 1937. / Summary also in English. Bibliography: p. [93]-95.

Thesis (M.Med.Sc.)--University of Hong Kong, 2003. / Includes bibliographical references (leaves 65-85). Also available in print.