Stürzbecher Lucas, Strauss Olaf
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental Ophthalmology, Berlin, Germany.
Eye Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Adv Exp Med Biol. 2025;1468:3-7. doi: 10.1007/978-3-031-76550-6_1.
In recent years, the adaptive immune system has gained a significant amount of attention due to its potential role in age-related macular degeneration (AMD). Orthologous approaches including cellular and animal models as well as pilot clinical trials have paved the way to understand the occurrence, alterations, and interactions of T cell populations in the retina. Interestingly, the notions of the involvement of the adaptive immune system in AMD have also gained support through recent findings in various neurodegenerative and chronic low-grade diseases, including multiple sclerosis, Parkinson's disease, or arteriosclerosis. In this group of pathologies, cells of the adaptive immune system bypass immune barriers and fuel inflammatory processes at immune-privileged sites. These findings have pointed at immunosenescence as a critical pro-inflammatory process involving T cell biology. Using a murine model relevant to the pathophysiology of geographic atrophy, we have demonstrated that specific populations of memory T cells are recruited to the retina prior to neurodegeneration. The investigation of these retinas at later degenerative stages revealed the presence of activated cytotoxic T cells at the injury site. These compelling results support the participation of the adaptive immune system in retina degeneration and highlight the potential of T cell populations as an early therapeutic target to slow the progression of AMD.
近年来,适应性免疫系统因其在年龄相关性黄斑变性(AMD)中的潜在作用而备受关注。包括细胞和动物模型以及初步临床试验在内的直系同源方法为理解视网膜中T细胞群体的发生、变化和相互作用铺平了道路。有趣的是,适应性免疫系统参与AMD的观点也通过最近在各种神经退行性疾病和慢性低度疾病(包括多发性硬化症、帕金森病或动脉硬化)中的发现得到了支持。在这组病理中,适应性免疫系统的细胞绕过免疫屏障,在免疫特权部位加剧炎症过程。这些发现指出免疫衰老作为涉及T细胞生物学的关键促炎过程。使用与地图状萎缩病理生理学相关的小鼠模型,我们已经证明特定群体的记忆T细胞在神经退行性变之前被募集到视网膜。在后期退行性阶段对这些视网膜的研究揭示了损伤部位存在活化的细胞毒性T细胞。这些令人信服的结果支持了适应性免疫系统参与视网膜变性,并突出了T细胞群体作为减缓AMD进展的早期治疗靶点的潜力。