Department of Chemistry and Biochemistry, The University of the Sciences in Philadelphia, Philadelphia, PA, United States.
Department of Physiological Genomics, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
Front Immunol. 2022 Jun 15;13:895519. doi: 10.3389/fimmu.2022.895519. eCollection 2022.
The cellular events that dictate the initiation of the complement pathway in ocular degeneration, such as age-related macular degeneration (AMD), is poorly understood. Using gene expression analysis (single cell and bulk), mass spectrometry, and immunohistochemistry, we dissected the role of multiple retinal and choroidal cell types in determining the complement homeostasis. Our scRNA-seq data show that the cellular response to early AMD is more robust in the choroid, particularly in fibroblasts, pericytes and endothelial cells. In late AMD, complement changes were more prominent in the retina especially with the expression of the classical pathway initiators. Notably, we found a spatial preference for these differences. Overall, this study provides insights into the heterogeneity of cellular responses for complement expression and the cooperation of neighboring cells to complete the pathway in healthy and AMD eyes. Further, our findings provide new cellular targets for therapies directed at complement.
细胞事件决定了补体途径在眼部变性中的启动，例如年龄相关性黄斑变性（AMD），但这一过程的机制尚不清楚。我们使用基因表达分析（单细胞和批量）、质谱和免疫组织化学，剖析了多种视网膜和脉络膜细胞类型在决定补体动态平衡中的作用。我们的 scRNA-seq 数据显示，早期 AMD 时，脉络膜中的细胞反应更为强烈，尤其是成纤维细胞、周细胞和内皮细胞。在晚期 AMD 中，补体变化更为明显，特别是经典途径起始因子的表达。值得注意的是，我们发现这些差异存在空间偏好。总的来说，这项研究深入了解了补体表达的细胞反应异质性以及相邻细胞之间的合作，以在健康和 AMD 眼中完成补体途径。此外，我们的研究结果为针对补体的治疗提供了新的细胞靶点。
