Kurzfassung

Glaucoma is a group of ocular disorders characterized by a progressive loss of retinal ganglion cells, optic nerve degeneration, and a gradual loss of visual field, which may ultimately lead to blindness. Worldwide there are approximately 60 million affected people, but the pathogenesis of glaucoma is only in part explored and understood. An elevated intraocular pressure (IOP) is considered a major
risk factor, but is not solely responsible for the disease. There are about 30% of glaucoma...Glaucoma is a group of ocular disorders characterized by a progressive loss of retinal ganglion cells, optic nerve degeneration, and a gradual loss of visual field, which may ultimately lead to blindness. Worldwide there are approximately 60 million affected people, but the pathogenesis of glaucoma is only in part explored and understood. An elevated intraocular pressure (IOP) is considered a major
risk factor, but is not solely responsible for the disease. There are about 30% of glaucoma patients who never had increased IOP. This form of glaucoma is called normal tension glaucoma (NTG). Several studies point towards an autoimmune involvement in glaucoma pathogenesis. Compared to controls elevated but also decreased serum IgG autoantibody reactivities could be observed in NTG patients as well as differing reactivities in patients with open angle glaucoma (POAG). These results were mainly generated by western blots and mass spectrometry.
Here we aim for detecting novel antibody-antigen complexes in sera of NTG patients via a beadbased immunoprecipitation method, and for identifying corresponding antigens through mass spectrometry. Subsequently a highly specific protein microarray approach will be used to screen NTG serum samples and generate detailed antibody patterns specific for NTG. We will comprise 180
serum samples of NTG patients and 180 control sera from a German and a US American population, therewith the identified antibody patterns become more objective. The newly detected as well as preselected purified antigens will be spotted onto microarray surfaces and incubated with patient or control sera. We will conduct a detailed microarray analysis of the antibody classes IgM and IgG with
its subclasses IgG1-4 using fluorescent secondary antibodies for differentiation. Generated data will be compared to the results of a POAG serum screening in order to detect differences and similarities, which are important for accurate diagnostic purposes. Furthermore we will analyze the immunoproteomic data in consideration of detailed clinical parameters to check for a potential correlation of specific antibody profiles and distinct clinical findings. The relevance of the analysis of IgM and the IgG subclasses is given by their different abilities to trigger the complement system, which is proven to be involved in retinal ganglion cell loss of
glaucoma patients. Comparing the antibody reactivity of the IgM/G subclasses in NTG patients and healthy subjects, we want to find out, if autoantibodies with a strong capacity for triggering the complement system show changed reactivities in glaucoma subjects. If so, this might be an explanation for the increased neurodegenerative activity of the complement system in the retina of glaucoma patients. Thus, the results might shed light on the involvement of changed autoantibody reactivities in NTG.» weiterlesen» einklappen