Prostaglandins (PG) play a major role in many endogenous processes including inflammation, labor, reproduction, and blood clotting. In the last two decades, these lipid signaling molecules have shown great potential as ocular hypotensive agents. Intraocular pressure (IOP) is a major risk factor in primary open-angled glaucoma (POAG), the second leading cause of blindness world-wide. Currently, prostaglandin F(2α) analogues are the most widely prescribed medications used to treat ocular hypertension. Studies have identified that almost all prostaglandin analogues exhibit anti-hypertensive effects in the eye, although they are not clinically available. Initial studies attributed the decrease in IOP observed to changes in hydraulic conductivity across the pressure-independent or uveoscleral pathway. More recent studies have shown that prostaglandin F(2α) analogues also lower IOP by affecting the pressure-dependent or trabecular pathway--the diseased tissue in POAG. Little is currently known about PG endogenous function, or the etiology of POAG. However, these studies suggest prostaglandin involvement in the maintenance of IOP in humans and identify the potential of PG analogues to treatment ocular hypertension. The research and findings presented in this dissertation address three specific aims designed to test the hypothesis that Endogenous prostaglandins, prostaglandin enzymes and prostaglandin receptors are involved in regulating conventional outflow facility. Specific aim 1 characterizes the distribution and activity of prostamide/prostaglandin F synthase (PM/PGFS) in the mouse and human eye using immunohistochemistry, western blot analysis and thin layer chromatography. Using techniques in biochemistry, molecular biology and physiology, specific aim 2, identifies the presence of the PG-EP₄ receptor within the outflow pathways, and the efficacy of a selective PG-EP₄ agonist, 3,7-dithiPGE₁, is also determined. Finally, specific aim 3 identifies PG-EP4 receptor coupling and downstream signaling using in vitro assays of transfected and primary cell lines to measure cAMP accumulation after treatment with a PG-EP₄ agonist. Collectively, these studies reveal the importance of PGE₂ synthesis and signaling to the conventional outflow pathway. They identify the PG-EP₄ receptor as a regulator of aqueous outflow and provide more specific therapeutic targets for the treatment of POAG.

Introduction Glaucoma presents an ever-increasing burden in Africa because of its asymptomatic nature. In South Africa, pseudoexfoliation syndrome (PXS) is particularly prevalent among black South Africans patients with glaucoma. The objective of the study was to determine the prevalence of PXS in a population of patients attending a glaucoma clinic; and to ascertain its clinical features. Materials and methods This was a cross-sectional survey of patients attending a glaucoma clinic in rural Eastern Cape. A sample of 100 patients were selected for the study and data was collected using a questionnaire and by doing a clinical examination. Data was analysed in Epi-info to determine prevalence, clinical features, and chi square test to determine association between PXS and socio-demographic factors and the severity of glaucoma. Results A total of 100 patients attending the clinic were included in the study. The majority of patients were male (59%); in their 60s; of rural origin (63%); and did not have any tertiary education (74%). Of note is that 84% of the patients had Primary Open Angle Glaucoma (POAG). The prevalence of pseudoexfoliation syndrome in these patients was 13%. All 13 PXS had the central round disc of PCE material on the lens capsule and a peripheral ban of PXS and a clear zone in between and PXS material was visible on the papillary margin in all cases. Conclusion This study shows a prevalence of 13% which is in keeping with other figures of previous South African studies which vary between 8.1% and 21.6%.

Kwong Man Kwong. / "June 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 114-141). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

No description available.

Fan Baojian. / "June 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 101-126). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

No description available.

Cellular responses to changes in pressure are implicated in numerous disease processes. In glaucoma apoptosis of retinal ganglion cells (RGCs) is associated with elevated intra-ocular pressure (IOP), however the exact cellular basis of this link remains unclear. This research aimed to examine the direct response of neuronal cells to elevated hydrostatic pressure in terms of apoptosis. We developed an in vitro model consisting of a pressure chamber to adjust ambient hydrostatic pressure, a source of neuronal cells and methods to measure apoptosis in these cells. The neural cells examined were primary retinal cultures, four neuronal cell lines (B35, PC12, C17, NT2), and the RGC-5 cell line. Pressure conditions selected were within physiological limits; 100 mmHg above atmospheric pressure (as seen clinically in severe acute glaucoma) and extended in RGC-5 neurons to 30 mmHg (chronic glaucoma) and 15 mmHg (normal IOP). Apoptosis was detected by cell morphology and specific immunochemical markers: TUNEL and Annexin V. Caspase-3 activation, a known pathway of apoptosis, was also investigated in RGC-5 neurons. These fluorescent markers were detected and quantified by automated Laser Scanning Cytometry. Negative controls were treated identically except for the application of pressure, while positive controls were generated by treatment with a known apoptotic stimulus. The results showed that neurons responded to elevated hydrostatic pressure directly and that an apoptotic process was induced. There was a greater level of apoptosis in pressurised cells compared to the negative controls. This apoptotic effect at high pressures was seen in primary rat retinal cultures and in both undifferentiated (B35, C17, NT2, RGC-5) and differentiated (PC12, RGC-5) neuronal cell lines. RGC-5 neurons showed a graded response, proportionate to the level of pressure elevation, representative of the severity of analogous clinical settings (acute, chronic glaucoma & normal). RGC-5 neurons also showed increased activation of Capsase-3. Thus this pathway may play a role in pressure induced apoptosis. Our findings indicate that pressure alone may act as a stimulus for apoptosis in neuronal cells. We suggest the possibility of novel mechanisms of pressure related mechanotransduction and cell death, relevant to the pathogenesis of glaucoma.

The overall goal of my work has been to gain a better understanding of Axenfeld-Rieger Syndrome (ARS), a human autosomal dominantly inherited mal-development of the anterior segment of the eye that is associated with glaucoma. By studying rare genetic causes of this complex disease we are gaining insight into the initial steps that ultimately lead to blindness. To achieve the goal of better understanding ARS, my research project had two parts. In the first part, I performed a retrospective clinical study in which I analyzed the glaucoma-related clinical presentation of ARS patients with FOXC1 and PITX2 defects. This study showed a good genotype-phenotype correlation which may be important for the physician in dealing with ARS patients. Patients with FOXC1 mutations had the mildest prognosis in glaucoma development, while patients with PITX2 defects and patients with FOXC1 duplication had a more severe prognosis in glaucoma development than patients with FOXC1 mutations. I tried to determine the best treatment for glaucoma in these patients. Unfortunately, in this study, current medical therapies did not successfully lower intraocular pressure or prevent progression of glaucoma in ARS patients with FOXC1 or PITX2 alterations. This clinical study also provided useful diagnostic criteria to identify the gene responsible for ARS. The second part of the project was to study the gene regulatory pathways of the PITX2 gene, mutations of which cause ARS. PITX2 is a transcription factor that regulates the expression of genes in the eye. The discovery of direct downstream targets of PITX2 is necessary for understanding the genetic mechanisms underlying complex, highly regulated processes such as development and underlying heritable human disorders. To find direct target genes of PITX2, I have used a recently developed method: the hormone receptor (HR)-inducible expression system for transcription factors coupled microarray analysis. The results obtained using this method have involved PITX2 in control of cellular stress. Recent investigations have suggested significant roles for cellular stress in glaucoma pathology. Understanding the control of these key aspects of cell function will have profound implications for understanding and treating the glaucoma that is the most clinically serious consequence of mutations of PITX2.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 180-186). Available also in a digital version from Dissertation Abstracts.

Glaucoma is a common disease that is difficult to diagnosis early using only visual field tests. Current research indicates that determination of retinal nerve fiber layer thickness (RNFLT) can serve as an early indicator of glaucoma [1]. RNFLT is measured by segmenting non-invasive optical coherence tomography images. However, high speckle noise and presence of artifacts in the images cause traditional layer detection and segmentation methods to fail. Multiphase active contours segmentation methods utilize region intensity and shape terms to produce multiple continuous boundaries simultaneously in noisy environments. A 2D and 3D multiphase active contours based algorithm was created to segment synthetic and real human retina OCT images. The 2D multiphase algorithm segmented eight simultaneous layers with a 3.14% mean A-scan error rate per layer. The 3D approach performed qualitatively accurate segmentation of a 20 image stack simultaneously. In an artificial, high-noise image stack the incorporation of more pixels per layer allowed improved segmentation using the 3D algorithm over the 2D. These results indicate that 2D and 3D multiphase active contours algorithms can be used to accurately segment retina layers. With further development to reduce computation time and automate initialization, these algorithms could be used to provide close to real-time clinical retinal image segmentation. / text