Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, 22060, Pakistan.
Department of Biosciences, COMSATS University Islamabad, Pakistan.
Curr Mol Med. 2019;19(10):705-718. doi: 10.2174/1566524019666190828150625.
Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis. Common genetic variants (with a minor allele frequency of >5% in the population) near the complement genes explain 40-60% of the heritability of AMD. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH, contribute to the formation of drusen and progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are normally involved in tissue remodeling also play a critical role in the pathogenesis of AMD. MMPs are involved in the degradation of cell debris and lipid deposits beneath retina but with age their functions get affected and result in the drusen formation, succeeding to macular degeneration. In this review, AMD pathology, existing knowledge about the normal and pathological role of complement system proteins and MMPs in the eye is reviewed. The scattered data of complement system proteins, MMPs, drusenogenesis, and lipofusogenesis have been gathered and discussed in detail. This might add new dimensions to the understanding of molecular mechanisms of AMD pathophysiology and might help in finding new therapeutic options for AMD.
年龄相关性黄斑变性（AMD）是一种主要影响 50 岁以上老年人的眼部疾病，其视网膜黄斑区退化，导致中心视力丧失。与 AMD 发病机制相关的主要因素有年龄、吸烟、饮食和遗传危险因素。AMD 发病机制中涉及一些相关的、合理的基因。在补体基因附近常见的遗传变异体（在人群中的次要等位基因频率>5%）解释了 AMD 遗传率的 40-60%。补体系统是一组协同作用以破坏外来入侵者、引发炎症并从细胞和组织中清除碎片的蛋白质。几个补体系统基因（包括 CFH）中的遗传变化导致了 drusen 的形成和 AMD 的进展。同样，通常参与组织重塑的基质金属蛋白酶（MMPs）在 AMD 的发病机制中也起着关键作用。MMPs 参与细胞碎片和视网膜下脂质沉积的降解，但随着年龄的增长，其功能受到影响，导致 drusen 形成，随后发展为黄斑变性。在这篇综述中，我们回顾了 AMD 的病理学，以及补体系统蛋白和 MMPs 在眼睛中的正常和病理作用的现有知识。我们详细收集和讨论了补体系统蛋白、MMPs、drusenogenesis 和 lipofusogenesis 的分散数据。这可能为理解 AMD 病理生理学的分子机制提供新的维度，并有助于为 AMD 寻找新的治疗选择。
