In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced
BackgroundThe 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 lea...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1296178/full |
| _version_ | 1797271397240668160 |
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| author | Sabrina Reinehr Julien Wulf Janine Theile Kim K. Schulte Marcus Peters Rudolf Fuchshofer H. Burkhard Dick Stephanie C. Joachim |
| author_facet | Sabrina Reinehr Julien Wulf Janine Theile Kim K. Schulte Marcus Peters Rudolf Fuchshofer H. Burkhard Dick Stephanie C. Joachim |
| author_sort | Sabrina Reinehr |
| collection | DOAJ |
| description | BackgroundThe 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.MethodsSix-week-old wildtype (WT+ONA) and βB1-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.ResultsWe 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.ConclusionThese 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. |
| first_indexed | 2024-03-07T14:03:06Z |
| format | Article |
| id | doaj.art-799de27d974245298b0db025ebd09068 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T14:03:06Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-799de27d974245298b0db025ebd090682024-03-07T05:01:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.12961781296178In a novel autoimmune and high-pressure glaucoma model a complex immune response is inducedSabrina Reinehr0Julien Wulf1Janine Theile2Kim K. Schulte3Marcus Peters4Rudolf Fuchshofer5H. Burkhard Dick6Stephanie C. Joachim7Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, GermanyDepartment of Molecular Immunology, Ruhr-University Bochum, Bochum, GermanyInstitute of Human Anatomy and Embryology, University Regensburg, Regensburg, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, GermanyBackgroundThe 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.MethodsSix-week-old wildtype (WT+ONA) and βB1-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.ResultsWe 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.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1296178/fullautoimmune glaucomacomplement systemmicroglia/macrophagesglaucoma animal modelsimmune responseintraocular pressure |
| spellingShingle | Sabrina Reinehr Julien Wulf Janine Theile Kim K. Schulte Marcus Peters Rudolf Fuchshofer H. Burkhard Dick Stephanie C. Joachim In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced Frontiers in Immunology autoimmune glaucoma complement system microglia/macrophages glaucoma animal models immune response intraocular pressure |
| title | In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced |
| title_full | In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced |
| title_fullStr | In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced |
| title_full_unstemmed | In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced |
| title_short | In a novel autoimmune and high-pressure glaucoma model a complex immune response is induced |
| title_sort | in a novel autoimmune and high pressure glaucoma model a complex immune response is induced |
| topic | autoimmune glaucoma complement system microglia/macrophages glaucoma animal models immune response intraocular pressure |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1296178/full |
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