Macrophage Plasticity and Function in the Eye and Heart

Macrophages are important mediators of inflammation and tissue remodeling. Recent insights into the heterogeneity of macrophage subpopulations have renewed interest in their functional diversity in homeostasis and disease. In addition, their plasticity enables them to perform a variety of functions in response to changing tissue contexts, such as those imposed by aging. These qualities make macrophages particularly intriguing cells given their dichotomous role in protecting against, or accelerating, diseases of the cardiovascular system and the eye, two tissues that are particularly susceptible to the effects of aging. We review novel perspectives on macrophage biology, as informed by recent studies detailing the diversity of macrophage identity and function, as well as mechanisms influencing macrophage behavior that might offer opportunities for new therapeutic strategies. Recent studies combining single-cell transcriptomics, imaging, and functional assays provide mechanistic validation of prior observations indicating that murine macrophage heterogeneity contributes to diverse roles in healthy tissue and during disease response.Disease models in mice have identified subpopulations of macrophages with characteristic gene expression and behavior profiles that protect against or exacerbate disease phenotypes in the cardiovascular system and the eye.Analysis of multiple macrophage populations can reveal molecular mechanisms of macrophage plasticity and phenotype switching (or lack thereof) in response to context-dependent tissue changes.Mechanistic insights from basic research have spurred numerous translational and clinical studies exploring the measurement or modulation of human macrophage function and identity in improving disease outcomes.