Microglia are immune cells in the central nervous system (CNS) that originate from the yolk sac in an embryo. The renewal of the microglia pool in the adult eye consists of two components. In addition to the self-proliferation of resident cells, microglia in the CNS also derive from the bone marrow (BM). BM-derived cells pass through the blood-brain barrier (BBB) or blood-retina barrier (BRB) and differentiate into microglia under specific conditions which involves a complex mechanism. Recent studies have widely investigated the role of resident microglia and BM-derived microglia in the retinal degenerative disease. Both two cell types play dual roles and share many similar functions. However, resident microglia tend to polarize to the M1 phenotype which is pro-inflammatory and neurotoxic, whereas BM-derived microglia mainly polarize to the neuroprotective M2 phenotype in retinal degeneration. The molecular mechanism that underlines the invasion of peripheral cells has led to extensive discussions. In addition to the BBB and BRB disruption, many signaling pathways are involved in this process. Based on these studies, we discuss the roles of these two types of microglia in retinal degeneration disease and the potential clinical application of BM-derived microglia, which may benefit future therapies.

Retinal degenerative disease (RDD) refers to a group of diseases with retinal degeneration that cause vision loss and affect people’s daily lives. Various therapies have been proposed, among which stem cell therapy (SCT) holds great promise for the treatment of RDDs. Microglia are immune cells in the retina that have two activation phenotypes, namely, pro-inflammatory M1 and anti-inflammatory M2 phenotypes. These cells play an important role in the pathological progression of RDDs, especially in terms of retinal inflammation. Recent studies have extensively investigated the therapeutic potential of stem cell therapy in treating RDDs, including the immunomodulatory effects targeting microglia. In this review, we substantially summarized the characteristics of RDDs and microglia, discussed the microglial changes and phenotypic transformation of M1 microglia to M2 microglia after SCT, and proposed future directions for SCT in treating RDDs.