Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration
IntroductionAge-related macular degeneration (AMD) is a leading cause of blindness with limited treatment options. Dysfunction of the retinal pigment epithelium (RPE) is a unifying salient feature of the pathology and a primary end-point damage leading to complications such as geographic atrophy (GA...
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Frontiers Media S.A.
2025-02-01
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| author | Lucas Stürzbecher Lucas Stürzbecher Lucas Stürzbecher Lucas Stürzbecher Hendrik Bartolomaeus Hendrik Bartolomaeus Hendrik Bartolomaeus Hendrik Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Sylvia Bolz Andjela Sekulic Marius Ueffing Marius Ueffing Simon J. Clark Simon J. Clark Simon J. Clark Nadine Reichhart Sergio Crespo-Garcia Nicola Wilck Nicola Wilck Nicola Wilck Nicola Wilck Olaf Strauß |
| author_facet | Lucas Stürzbecher Lucas Stürzbecher Lucas Stürzbecher Lucas Stürzbecher Hendrik Bartolomaeus Hendrik Bartolomaeus Hendrik Bartolomaeus Hendrik Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Sylvia Bolz Andjela Sekulic Marius Ueffing Marius Ueffing Simon J. Clark Simon J. Clark Simon J. Clark Nadine Reichhart Sergio Crespo-Garcia Nicola Wilck Nicola Wilck Nicola Wilck Nicola Wilck Olaf Strauß |
| author_sort | Lucas Stürzbecher |
| collection | DOAJ |
| description | IntroductionAge-related macular degeneration (AMD) is a leading cause of blindness with limited treatment options. Dysfunction of the retinal pigment epithelium (RPE) is a unifying salient feature of the pathology and a primary end-point damage leading to complications such as geographic atrophy (GA), which represents the most common end-stage of AMD.MethodsHuman and murine ocular tissues were used for histological examinations. Furthermore, flow cytometry and gene expression analysis were used on ocular and splenic tissues of Cx3cr1GFP/GFP and C57BL/6J mice at 8 and 12 months of age to characterize the dynamics of local and systemic T cell populations.ResultsWe show the presence of memory T cells such as CD45RO+ cells in the choroid and retina of patients with AMD with a peak of abundance in early stages of AMD. As further evidence for the contribution of the adaptive immune system to GA we identified an increased frequency of CD44+ CD69+ KLRG1+ T cells and para-inflammation of the retina in a mouse model that mimics features of GA. Importantly, the activation of T cells found at early AMD-like stages prior to degeneration possessed long-lasting cytotoxic properties and adopted typical features of senescent immune cells. T cells were intimately associated with the RPE, suggesting transmigration and participating in local micro-inflammation.DiscussionOur data support that activation and accumulation of memory T cells can be considered as a hallmark of early AMD, and that adaptive immunosenescence likely to contribute to the chronic inflammation associated with RPE damage and the progression to large lesions as seen in GA. |
| format | Article |
| id | doaj-art-9ad5af8820e0486c8f283ef82697a76b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-9ad5af8820e0486c8f283ef82697a76b2025-02-05T07:32:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15201881520188Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degenerationLucas Stürzbecher0Lucas Stürzbecher1Lucas Stürzbecher2Lucas Stürzbecher3Hendrik Bartolomaeus4Hendrik Bartolomaeus5Hendrik Bartolomaeus6Hendrik Bartolomaeus7Theda U. P. Bartolomaeus8Theda U. P. Bartolomaeus9Theda U. P. Bartolomaeus10Theda U. P. Bartolomaeus11Sylvia Bolz12Andjela Sekulic13Marius Ueffing14Marius Ueffing15Simon J. Clark16Simon J. Clark17Simon J. Clark18Nadine Reichhart19Sergio Crespo-Garcia20Nicola Wilck21Nicola Wilck22Nicola Wilck23Nicola Wilck24Olaf Strauß25Experimental Ophthalmology, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt Universität zu Berlin, Berlin, GermanyExperimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyEye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, GermanyExperimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, GermanyInstitute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, GermanyExperimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, GermanyCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of Tübingen, Tübingen, GermanyExperimental Ophthalmology, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt Universität zu Berlin, Berlin, GermanyInstitute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment for Ophthalmology, University Eye Clinic, Eberhard Karls University of Tübingen, Tübingen, GermanyInstitute for Ophthalmic Research, Department for Ophthalmology, Eberhard Karls University of Tübingen, Tübingen, GermanyDepartment for Ophthalmology, University Eye Clinic, Eberhard Karls University of Tübingen, Tübingen, Germany0Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United KingdomExperimental Ophthalmology, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt Universität zu Berlin, Berlin, Germany1École d’optométrie, University of Montreal, Montréal, QC, CanadaExperimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, GermanyMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany2Department of Nephrology and Internal Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyExperimental Ophthalmology, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt Universität zu Berlin, Berlin, GermanyIntroductionAge-related macular degeneration (AMD) is a leading cause of blindness with limited treatment options. Dysfunction of the retinal pigment epithelium (RPE) is a unifying salient feature of the pathology and a primary end-point damage leading to complications such as geographic atrophy (GA), which represents the most common end-stage of AMD.MethodsHuman and murine ocular tissues were used for histological examinations. Furthermore, flow cytometry and gene expression analysis were used on ocular and splenic tissues of Cx3cr1GFP/GFP and C57BL/6J mice at 8 and 12 months of age to characterize the dynamics of local and systemic T cell populations.ResultsWe show the presence of memory T cells such as CD45RO+ cells in the choroid and retina of patients with AMD with a peak of abundance in early stages of AMD. As further evidence for the contribution of the adaptive immune system to GA we identified an increased frequency of CD44+ CD69+ KLRG1+ T cells and para-inflammation of the retina in a mouse model that mimics features of GA. Importantly, the activation of T cells found at early AMD-like stages prior to degeneration possessed long-lasting cytotoxic properties and adopted typical features of senescent immune cells. T cells were intimately associated with the RPE, suggesting transmigration and participating in local micro-inflammation.DiscussionOur data support that activation and accumulation of memory T cells can be considered as a hallmark of early AMD, and that adaptive immunosenescence likely to contribute to the chronic inflammation associated with RPE damage and the progression to large lesions as seen in GA.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1520188/fullage related macular degenerationgeographic atrophyT cellsadaptive immune systemneurodegeneration |
| spellingShingle | Lucas Stürzbecher Lucas Stürzbecher Lucas Stürzbecher Lucas Stürzbecher Hendrik Bartolomaeus Hendrik Bartolomaeus Hendrik Bartolomaeus Hendrik Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Theda U. P. Bartolomaeus Sylvia Bolz Andjela Sekulic Marius Ueffing Marius Ueffing Simon J. Clark Simon J. Clark Simon J. Clark Nadine Reichhart Sergio Crespo-Garcia Nicola Wilck Nicola Wilck Nicola Wilck Nicola Wilck Olaf Strauß Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration Frontiers in Immunology age related macular degeneration geographic atrophy T cells adaptive immune system neurodegeneration |
| title | Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration |
| title_full | Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration |
| title_fullStr | Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration |
| title_full_unstemmed | Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration |
| title_short | Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration |
| title_sort | outer retina micro inflammation is driven by t cell responses prior to retinal degeneration in early age related macular degeneration |
| topic | age related macular degeneration geographic atrophy T cells adaptive immune system neurodegeneration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1520188/full |
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