In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced.

Background: The neurodegenerative processes leading to glaucoma are complex. In addition to elevated intraocular pressure (IOP), an involvement of immunological mechanisms is most likely. In the new multifactorial glaucoma model, a combination of high IOP and optic nerve antigen (ONA) immunization leads to an enhanced loss of retinal ganglion cells accompanied by a higher number of microglia/macrophages in the inner retina. Here, we aimed to evaluate the immune response in this new model, especially the complement activation and the number of T-cells, for the first time. Further, the microglia/macrophage response was examined in more detail. Methods: Six-week-old wildtype (WT+ONA) and ßB1-connective tissue growth factor high-pressure mice (CTGF+ONA) were immunized with 1 mg ONA. A wildtype control (WT) and a CTGF group (CTGF) received NaCl instead. Six weeks after immunization, retinae from all four groups were processed for immunohistology, RT-qPCR, and flow cytometry, while serum was used for microarray analyses. Results: We noticed elevated numbers of C1q+ cells (classical complement pathway) in CTGF and CTGF+ONA retinae as well as an upregulation of C1qa, C1qb, and C1qc mRNA levels in these groups. While the complement C3 was only increased in CTGF and CTGF+ONA retinae, enhanced numbers of the terminal membrane attack complex were noted in all three glaucoma groups. Flow cytometry and RT-qPCR analyses revealed an enhancement of different microglia/macrophages markers, including CD11b, especially in CTGF and CTGF+ONA retinae. Interestingly, increased retinal mRNA as well as serum levels of the tumor necrosis factor α were found throughout the different glaucoma groups. Lastly, more T-cells could be observed in the ganglion cell layer of the new CTGF+ONA model. Conclusion: These results emphasize an involvement of the complement system, microglia/macrophages, and T-cells in glaucomatous disease. Moreover, in the new multifactorial glaucoma model, increased IOP in combination with autoimmune processes seem to enforce an additional T-cell response, leading to a more persistent pathology. Hence, this new model mimics the pathomechanisms occurring in human glaucoma more accurately and could therefore be a helpful tool to find new therapeutic approaches for patients in the future.

A dual-phase xenon TPC for scintillation and ionisation yield measurements in liquid xenon.

A small-scale, two-phase (liquid/gas) xenon time projection chamber (Xurich II) was designed, constructed and is under operation at the University of Zürich. Its main purpose is to investigate the microphysics of particle interactions in liquid xenon at energies below 50 keV, which are relevant for rare event searches using xenon as target material. Here we describe in detail the detector, its associated infrastructure, and the signal identification algorithm developed for processing and analysing the data. We present the first characterisation of the new instrument with calibration data from an internal 83 m Kr source. The zero-field light yield is 15.0 and 14.0 photoelectrons/keV at 9.4 and 32.1 keV, respectively, and the corresponding values at an electron drift field of 1 kV/cm are 10.8 and 7.9 photoelectrons/keV. The charge yields at these energies are 28 and 31 electrons/keV, with the proportional scintillation yield of 24 photoelectrons per one electron extracted into the gas phase, and an electron lifetime of 200  µ s. The relative energy resolution, σ / E , is 11.9 and 5.8% at 9.4 and 32.1 keV, respectively using a linear combination of the scintillation and ionisation signals. We conclude with measurements of the electron drift velocity at various electric fields, and compare these to literature values.