The role of immune modulators in age-related macular degeneration

Highlights•IL-1β, IL-6, IL-8, IL-18, TNF-α, and MCP-1 are the most extensively characterised cytokines/chemokines in the context of AMD.•A wide range of immune modulators are implicated in the pathophysiology of AMD.•Several immune modulators, especially with proinflammatory function, are elevated in the systemic circulation in AMD.AbstractWe provide an overview of the expanding literature on the role of cytokines and immune mediators in pathophysiology of age-related macular degeneration (AMD). Although many immunological mediators have been linked to AMD pathophysiology, the broader mechanistic picture remains unclear with substantial variations in the levels of evidence supporting these mediators. Therefore, we reviewed the literature considering the varying levels of supporting evidence. A Medical Subject Headings (MeSH) term-based literature research was conducted in September, 2023, consisting of the MeSH terms "cytokine" and "Age-related macular degeneration" connected by the operator "AND". After screening the publications by title, abstract, and full text, a total of 146 publications were included. The proinflammatory cytokines IL-1β (especially in basic research studies), IL-6, IL-8, IL-18, TNF-α, and MCP-1 are the most extensively characterised cytokines/chemokines, highlighting the role of local inflammasome activation and altered macrophage function in the AMD pathophysiology. Among the antiinflammatory mediators IL-4, IL-10, and TGF-β were found to be the most extensively characterised, with IL-4 driving and IL-10 and TGF-β suppressing disease progression. Despite the extensive literature on this topic, a profound understanding of AMD pathophysiology has not yet been achieved. Therefore, further studies are needed to identify potential therapeutic targets, followed by clinical studies