The role of NAD plus metabolism in macrophages in age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of legal blindness and moderate and severe vision impairment (MSVI) in people older than 50 years. It is classified in various stages including early, intermediate, and late stage. In the early stages, innate immune system, especially macrophages, play an essential part in disease onset and progression. NAD+ is an essential coenzyme involved in cellular senescence and immune cell function, and its role in age-related diseases is gaining increasing attention. The imbalance between the NAD+ synthesis and consumption causes the fluctuation of intracellular NAD+ level which determines the polarization fate of macrophages. In AMD, the over-expression of NAD+-consuming enzymes in macrophages leads to declining of NAD+ concentrations in the microenvironment. This phenomenon triggers the activation of inflammatory pathways in macrophages, positive feedback aggregation of inflammatory cells and accumulation of reactive oxygen species (ROS). This review details the role of NAD+ metabolism in macrophages and molecular mechanisms during AMD. The selected pathways were identified as potential targets for intervention in AMD, pending further investigation.