Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA.
Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA; Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Division of Research, Charleston, SC, USA.
Exp Eye Res. 2022 Sep;222:109164. doi: 10.1016/j.exer.2022.109164. Epub 2022 Jul 4.
The extracellular matrix (ECM) and its turnover play a crucial role in the pathogenesis of several inflammatory diseases, including age-related macular degeneration (AMD). Elastin, a critical protein component of the ECM, not only provides structural and mechanical support to tissues, but also mediates several intracellular and extracellular molecular signaling pathways. Abnormal turnover of elastin has pathological implications. In the eye elastin is a major structural component of Bruch's membrane (BrM), a critical ECM structure separating the retinal pigment epithelium (RPE) from the choriocapillaris. Reduced integrity of macular BrM elastin, increased serum levels of elastin-derived peptides (EDPs), and elevated elastin antibodies have been reported in AMD. Existing reports suggest that elastases, the elastin-degrading enzymes secreted by RPE, infiltrating macrophages or neutrophils could be involved in BrM elastin degradation, thus contributing to AMD pathogenesis. EDPs derived from elastin degradation can increase inflammatory and angiogenic responses in tissues, and the elastin antibodies are shown to play roles in immune cell activity and complement activation. This review summarizes our current understanding on the elastases/elastin fragments-mediated mechanisms of AMD pathogenesis.
细胞外基质（ECM）及其代谢在几种炎症性疾病的发病机制中起着关键作用，包括年龄相关性黄斑变性（AMD）。弹性蛋白是 ECM 的关键蛋白成分，不仅为组织提供结构和机械支撑，还介导几种细胞内和细胞外的分子信号通路。弹性蛋白的异常代谢与病理学有关。在眼睛中，弹性蛋白是布鲁赫膜（BrM）的主要结构成分，BrM 是一种关键的 ECM 结构，将视网膜色素上皮（RPE）与脉络膜毛细血管分开。AMD 患者的黄斑 BrM 弹性蛋白完整性降低、血清弹性蛋白衍生肽（EDP）水平升高和弹性蛋白抗体升高。现有报告表明，RPE、浸润的巨噬细胞或中性粒细胞分泌的弹性蛋白酶，即弹性蛋白降解酶，可能参与 BrM 弹性蛋白的降解，从而导致 AMD 的发病机制。源自弹性蛋白降解的 EDP 可增加组织中的炎症和血管生成反应，并且弹性蛋白抗体显示出在免疫细胞活性和补体激活中的作用。本综述总结了我们目前对 AMD 发病机制中弹性蛋白酶/弹性蛋白片段介导机制的理解。
