The roles of microglia in neural remodeling during retinal degeneration

Retina remodeling is a consequence of many retinal degenerative diseases that are characterized by progressive photoreceptor death. Retina remodeling involves a series of complex pathological processes, consisting of photoreceptor degeneration and death, as well as retinal cell reprogramming and "rewiring". This rewiring alters retinal neural circuits that are centered on synaptic connections and lead to widespread death of retinal cells. Retinal remodeling, especially inner retinal remodeling, is the major factor that limits the effectiveness of various treatment strategies, including cell therapy; thus, it is important to elucidate the mechanisms involved in retinal remodeling during retinal degeneration. Microglia are the dominant immune cells in the retina. Microglia monitor the retinal microenvironment, are activated following retinal injury or degeneration, have powerful phagocytosis capabilities, and play a critical role in synaptic pruning during central neural system development. Analogously, microglia have been found to participate in the clearance of synaptic elements in a complement-dependent manner in the classic retinitis pigmentosa (RP) model, Royal College of Surgeons (RCS) rats, and retard the formation of ectopic neuritogenesis and the deterioration of visual function during retinal degeneration. Since previous research on microglia has rarely concentrated on synaptic remodeling during retinal degeneration, summarizing the microglial mechanisms involved in retinal remodeling is necessary in order to design compounds targeting microglia and retinal remodeling that might be promising therapeutic strategies for treating retinal degeneration.