Reinehr, Sabrina and Wulf, Julien and Theile, Janine and Schulte, Kim K. and Peters, Marcus and Fuchshofer, Rudolf and Dick, H. Burkhard and Joachim, Stephanie C. (2024) In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced. FRONTIERS IN IMMUNOLOGY, 15: 1296178. ISSN 1664-3224
Full text not available from this repository. (Request a copy)Abstract
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 beta B1-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 alpha 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-ALPHA; RETINAL GANGLION-CELLS; OPEN-ANGLE GLAUCOMA; HUMAN TRABECULAR MESHWORK; OCULAR HYPERTENSION; AQUEOUS-HUMOR; T-CELLS; GENE-EXPRESSION; EX-VIVO; ACTIVATION; autoimmune glaucoma; complement system; microglia/macrophages; glaucoma animal models; immune response; intraocular pressure; retina; T-cells |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jan 2026 07:27 |
| Last Modified: | 28 Jan 2026 07:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64648 |
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