Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population.
Optimal vision requires a high-functioning central retina, in particular the photoreceptor-dense macula, which is responsible for the fine visual acuity that is required for tasks such as reading, facial recognition and driving. Age-related macular degeneration (AMD) refers to the progressive degeneration of the macula that commonly occurs in people over 60 years of age. More than 30 million individuals worldwide suffer from visual impairment as a result of AMD, which is estimated to account for more than US$300 billion in annual economic costs.
The study of AMD has, in many respects, been at the forefront of research into complex diseases. The discovery of the Tyr402His polymorphism of complement factor H (CFH) that confers increased statistical risk of developing AMD was the first of its kind for a complex disease. Furthermore, multiple biological therapies that target vascular endothelial growth factor A (VEGFA) in neovascular AMD (also known as exudative or ‘wet’ AMD) have recently revolutionized the clinical management of this disease. However, despite advances in the understanding, diagnosis and treatment of AMD in the past decade, disease prevalence increases with the ageing human population. The next decade will see a steady increase in the incidence and economic cost of AMD.
Despite the fact that AMD is presumed to have a multifaceted aetiology, immune dysfunction is a recurring theme in its pathogenesis. In this Review, we discuss the fundamental concepts and current ideas of AMD pathogenesis, with a particular focus on several recent advances in the immune aspects of the disease. We begin by describing the normal structure of the retina and the characteristic features of AMD. Next, we focus on the major immunological processes that have important roles in AMD development and we discuss the inflammatory component of neovascular AMD. We then present an integrated model of the immune modulation of AMD pathogenesis. Finally, we summarize the possibility of using immune-based therapeutics to prevent and treat AMD development. The aim of this Review is to present an up-to-date discussion of recent immunological findings in AMD. Consequently, we have condensed the discussion of the complement pathway, which is the most thoroughly studied immune pathway in AMD; for a more comprehensive summary of complement biology in AMD, the reader is referred to other reviews…..
Source: Stargardt Press