E-cadherin (E-CDH) is one of the most important cell surface glycoproteins involved in cell morphogenesis. In primary open angle glaucoma (POAG), the extracellular matrixes of trabecular meshwork and ...lamina cribrosa in the optic nerve head are out of balance. We suspected that E-CDH by way of metalloproteinases is closely related to POAG. We therefore investigated the relationship between CDH-1 gene 3' untranslated region (3'-UTR) polymorphism and POAG patients in order to support this hypothesis.
We enrolled 60 POAG patients and 103 healthy volunteers from the Department of Ophthalmology at the China Medical University Hospital, Taichung, Taiwan, ROC. None of the control subjects had a history of eye disease and all underwent the same examination as the POAG patients. PCR-based analysis of the restriction fragment length polymorphism was used to test the CDH-1 gene 3'-UTR polymorphism. All statistical analyses were performed by the chi(2) test.
There was a significant difference in the distribution of the CDH-1 gene 3'-UTR C/T polymorphism between POAG patients and the normal controls (p <0.000). The odds ratio of the 'C' allele was al so significantly different between both groups (odds ratio = 5.510, 95% confidence interval = 3.171-9.574).
CDH-1 is closely related to metalloproteinase and plays an important but not well-understood role in the onset and progression of POAG. The exact role of CDH-1 in POAG could be resolved by the posttranslated products of the gene and the protein-protein interaction of the gene products in the future.
BACKGROUNDFactors other than intraocular pressure are likely to play a role in the pathogenesis of glaucomatous optic neuropathy, particularly in individuals with normal tension glaucoma (NTG). ...Recent laboratory evidence has shown that there are potential similarities between Alzheimer disease and NTG in cellular apoptosis leading to neurodegeneration. IL-1α (−889) T allele polymorphism has been found to increase the risk of developing Alzheimer disease. The aim of this study was to test in a Chinese cohort the hypothesis that IL-1α (−889) polymorphism is associated with NTG.
METHODSOne hundred sixty-two unrelated patients with NTG were recruited and compared with 167 controls in a Chinese population. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique. Patients and controls were genotyped for the C/T polymorphism at position −889 of the IL-1α gene promoter region.
RESULTSThere was no significant difference in the frequency of IL-1α (−889) alleles or genotypes in the NTG population compared with that in the control group.
CONCLUSIONSWe conclude that C/T polymorphism at position −889 of the IL-1α gene promoter region does not increase the risk of developing NTG. However, further studies on NTG are necessary to investigate the genetic basis and factors involved in the development of the neurodegenerative process.
A high concentration of glutamate in the eyes not only activates N-methyl-D-aspartate (NMDA) receptors, but also is toxic to the retina ganglion cells (RGCs) in glaucomatous patients. Our previous ...study had found that aloe-emodin sulfates/glucuronides metabolites, an anthraquinone polyphenol, exerted a neuroprotective activity upon RGCs. In order to understand the mechanisms involved in this neuroprotective effect, this study aimed to determine the expressions of RNAs and proteins in various treatments. The proteins expressed in the control group, NMDA-treated group, and aloe-emodin metabolites-cotreated group were separated by two-dimensional gel electrophoresis (2-DE). Protein spots were excised from 2-DE and analyzed by nano-LC-MS/MS (nano-liquid chromatography with mass spectrometry; tandem MS). Quantitative polymerase chain reaction (Q-PCR) was used to investigate the RNA related to these proteins. There were 84 spots with significant differences in various treatments. Among the 84 spots, we identified 9 spots whose functions were closely related to regulate the apoptosis of cells. The results of Q-PCR were not completely unanimous with those of 2-DE. Our results suggested that aloe-emodin metabolites decreased NMDA-induced apoptosis of RGCs by preserving, and inducing, some proteins related to the antioxidation and regulation of cells' energy. Both the level of RNA and protein of superoxide dismutase (Cu-Zn) were significantly elevated after aloe-emodin metabolites were added. The mechanisms of neuroprotection are complicated, and involve not only the transcription and stability of mRNA, but also post-translation protein modifications, degradation, and protein-protein interaction.
The cell polarity gene, crumbs(crb), has been shown to participate in the development and degeneration of the Drosophila retina. Mutations in CRB1, the human homologue of Drosophilacrb, also result ...in retinitis pigmentosa and Leber congential amaurosis. In this study, we used the gain-of-function approach to delineate the roles of crb in developing Drosophila eye. In the third-instar larval stage, eye development is initiated with photoreceptor differentiation and positioning of photoreceptor nuclei in the apical cellular compartment of retinal epithelium. In the pupal stage, differentiated photoreceptors begin to form the photosensitive structures, the rhabdomeres, at their apical surface. Using GMR-Gal4 to drive overexpression of the Crb protein at the third-instar eye disc, we found that differentiation of photoreceptors was disrupted and the nuclei of differentiated photoreceptors failed to occupy the apical compartment. Using hs-Gal4 to drive Crb overexpression in pupal eyes resulted in interference with extension of the adherens junctions and construction of the rhabdomeres, and these defects were stage-dependent. This gain-of-function study has enabled us to delineate the roles of Crb at selective stages of eye development in Drosophila.
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