Age-related macular degeneration (AMD) remains a leading cause of vision loss in elderly patients. Its etiology and progression are, however, deeply intertwined with various cellular and molecular interactions within the retina and choroid. Among the key cellular players least studied are choroidal mast cells, with important roles in immune and allergic responses. Here, we will review what is known regarding the pathophysiology of AMD and expand on the recently proposed intricate roles of choroidal mast cells and their activation in outer retinal degeneration and AMD pathogenesis. We will focus on choroidal mast cell activation, the release of their bioactive mediators, and potential impact on ocular oxidative stress, inflammation, and overall retinal and choroidal health. We propose an important role for thrombospondin-1 (TSP1), a major ocular angioinflammatory factor, in regulation of choroidal mast cell homeostasis and activation in AMD pathogenesis. Drawing from limited studies, this review underscores the need for further comprehensive studies aimed at understanding the precise roles changes in TSP1 levels and choroidal mast cell activity play in pathophysiology of AMD. We will also propose potential therapeutic strategies targeting these regulatory pathways, and highlighting the promise they hold for curbing AMD progression through modulation of mast cell activity. In conclusion, the evolving understanding of the role of choroidal mast cells in AMD pathogenesis will not only offer deeper insights into the underlying mechanisms but will also offer opportunities for development of novel preventive strategies.
Keywords: choroidal neovascularization; fibrosis; inflammation; mast cells; oxidative stress; retinal degeneration; retinal pigment epithelium.