Kim Benjamin J, Liu Tianyu, Mastellos Dimitrios C, Lambris John D
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Semin Immunol. 2022 Jan;59:101633. doi: 10.1016/j.smim.2022.101633. Epub 2022 Jul 2.
The eye presents a unique opportunity for complement component 3 (C3) therapeutics. Drugs can be delivered directly to specific parts of the eye, and growing evidence has established a pivotal role for C3 in age-related macular degeneration (AMD). Emerging data show that C3 may be important to the pathophysiology of other eye diseases as well. This article will discuss the location of C3 expression in the eye as well as the preclinical and clinical data regarding C3's functions in AMD. We will provide a comprehensive review of developing C3 inhibitors for the eye, including the Phase 2 and 3 data for the C3 inhibitor pegcetacoplan as a treatment for the geographic atrophy of AMD. Developing evidence also points toward C3 as a therapeutic target for stages of AMD preceding geographic atrophy. We will also discuss data illuminating C3's relationship to other eye diseases, such as Stargardt disease, diabetic retinopathy, and glaucoma. In addition to being a converging point and centerpiece of the complement cascade, C3 has broad effects as a multifaceted controller of opsonophagocytosis, microglia/macrophage recruitment, and downstream terminal pathway activity. C3 is a crucial player in the pathophysiology of AMD but also seems to have importance in other diseases that are major causes of blindness. Directions for further investigation will be highlighted, as culminating evidence suggests that we may be approaching an era of C3 therapeutics for the eye.
眼睛为补体成分3（C3）治疗提供了独特的契机。药物可直接递送至眼睛的特定部位，越来越多的证据表明C3在年龄相关性黄斑变性（AMD）中起关键作用。新出现的数据表明，C3对其他眼部疾病的病理生理学可能也很重要。本文将讨论C3在眼中的表达位置，以及有关C3在AMD中功能的临床前和临床数据。我们将全面综述针对眼部开发C3抑制剂的情况，包括C3抑制剂聚乙二醇乙酰半胱氨酸作为治疗AMD地图样萎缩的2期和3期数据。越来越多的证据还表明，C3是AMD地图样萎缩之前各阶段的治疗靶点。我们还将讨论阐明C3与其他眼部疾病（如斯塔加特病、糖尿病视网膜病变和青光眼）关系的数据。除了作为补体级联反应的汇聚点和核心成分外，C3作为调理吞噬作用、小胶质细胞/巨噬细胞募集及下游终末途径活性的多方面调控因子具有广泛作用。C3是AMD病理生理学中的关键因素，但似乎在其他主要致盲疾病中也很重要。将强调进一步研究的方向，因为最终证据表明我们可能正迈向眼部C3治疗的时代。
