Age-related macular degeneration is a neuroinflammatory disease that is the leading cause of blindness worldwide. In addition to mutations in immune-related genes, it is caused by the accumulation of environmental factors such as obesity and other inflammatory triggers with age. We have found that the past histories of obesity and infections can lead to immunological reprogramming in the innate immune system and affect the development of age-related macular degeneration in later life. This reveals a new link in the role of innate immune memory in neuroinflammatory diseases, and intervention in innate immune memory may be a new therapeutic strategy.