Retinal degenerative diseases: Complement system-microglia crosstalk

Retinal degenerative diseases (RDD) are a group of age-related blinding eye diseases characterized by progressive degeneration and functional impairment of retinal photoreceptors or ganglion cells, for which there are currently no effective treatments. The complement system is an important innate immune system in the human body, activated through 3 pathways (classical pathway, lectin pathway, and alternative pathway) to ultimately form a membrane attack complex that acts on target cells. Microglia are the innate immune cells of the retina, responsible for maintaining retinal homeostasis. Complement system activation and microglial activation have been identified in RDD. Complement activation products C3 and C5 generate anaphylatoxins C3a and C5a, whose receptors C3aR and C5aR1 can activate microglia. Activated microglia can further produce complement C1q to activate the complement system, forming a positive feedback loop that exacerbates retinal damage. In this review, we focus on the crosstalk between the complement system and microglia in age-related macular degeneration, diabetic retinopathy, glaucoma, and pathological myopia-related retinal degeneration, and summarize clinical studies targeting the complement system and microglia for the treatment of RDD.