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| Item Type: | Article |
|---|---|
| Title: | Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration |
| Creators Name: | Stürzbecher, L., Bartolomaeus, H., Bartolomaeus, T.U.P., Bolz, S., Sekulic, A., Ueffing, M., Clark, S.J., Reichhart, N., Crespo-Garcia, S., Wilck, N. and Strauß, O. |
| Abstract: | INTRODUCTION: Age-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. METHODS: Human and murine ocular tissues were used for histological examinations. Furthermore, flow cytometry and gene expression analysis were used on ocular and splenic tissues of Cx3cr1(GFP/GFP) and C57BL/6J mice at 8 and 12 months of age to characterize the dynamics of local and systemic T cell populations. RESULTS: We 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. DISCUSSION: Our 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. |
| Keywords: | Age Related Macular Degeneration, Geographic Atrophy, T Cells, Adaptive Immune System, Neurodegeneration, Animals, Mice |
| Source: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Publisher: | Frontiers Media SA |
| Volume: | 16 |
| Page Range: | 1520188 |
| Date: | 5 February 2025 |
| Official Publication: | https://doi.org/10.3389/fimmu.2025.1520188 |
| PubMed: | View item in PubMed |
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