table_2_Dynamic Interplay of Innate and Adaptive Immunity During Sterile Retinal Inflammation: Insights From the Transcriptome.xlsx

The pathogenesis of many retinal degenerations, such as age-related macular degeneration (AMD), is punctuated by an ill-defined network of sterile inflammatory responses. The delineation of innate and adaptive immune milieu among the broad leukocyte infiltrate, and the gene networks, which construct these responses, are poorly described in the eye. Using photo-oxidative damage in a rodent model of subretinal inflammation, we employed a novel RNA-sequencing framework to map the global gene network signature of retinal leukocytes. This revealed a previously uncharted interplay of adaptive immunity during subretinal inflammation, including prolonged enrichment of myeloid and lymphocyte migration, antigen presentation, and the alternative arm of the complement cascade involving Factor B. We demonstrate Factor B-deficient mice are protected against macrophage infiltration and subretinal inflammation. Suppressing the drivers of retinal leukocyte proliferation, or their capacity to elicit complement responses, may help preserve retinal structure and function during sterile inflammation in diseases such as AMD.

多种视网膜退行性疾病（如年龄相关性黄斑变性（age-related macular degeneration，AMD））的发病进程，均由一套尚未阐明的无菌性炎症反应网络所主导。目前对于眼部广泛白细胞浸润中的先天与适应性免疫微环境，以及介导此类炎症反应的基因调控网络，学界的解析仍存在显著空白。本研究通过光氧化损伤构建视网膜下炎症啮齿动物模型，采用新型RNA测序（RNA-sequencing）分析框架，绘制了视网膜白细胞的全局基因网络特征图谱。该分析揭示了视网膜下炎症过程中此前未被发现的适应性免疫互作网络，包括髓系细胞与淋巴细胞迁移、抗原呈递的持续富集，以及涉及B因子（Factor B）的补体级联旁路激活通路。本研究证实，B因子缺陷型小鼠可免受巨噬细胞浸润与视网膜下炎症的影响。靶向抑制视网膜白细胞增殖的驱动因素，或其触发补体级联反应的能力，或可在AMD等疾病的无菌性炎症进程中，帮助维持视网膜的结构与功能。