Characteristics of bone marrow-derived microglia in the normal and injured retina

PURPOSE. To compare the distribution and immunologic characteristics of bone marrow (BM)-derived and resident microglia in the retina. METHODS. Mice were irradiated and injected with enhanced green fluorescent protein-positive (EGFP(+)) BM cells. One month to 12 months after BM transplantation, eyes were analyzed histologically for the expression of EGFP and various monocyte/microglia/macrophage markers (Iba-1, F4/80, GS-1, major histocompatibility complex [MHC] class II). N-methyl-N-nitrosourea (MNU) was injected or retinal detachment was created to induce retinal damage. RESULTS. Many BM-derived EGFP(+) cells were found in the ciliary body and choroid and around the optic nerve in the uninjured eyes. Within the retina, few such cells existed at the retinal margin and juxtapapillary area at 3 to 12 months after BM transplantation. However, after MNU injection, many EGFP+ cells were found in the retina adjacent to the retinal vessels, optic nerve, and ciliary body that rapidly spread throughout the retina. Most of them showed morphologic and immunohistochemical features of microglia. By 7 days after MNU injection, EGFP(+) BM-derived cells occupied approximately 15% of the total Iba-1(+) retinal microglia. Meanwhile, the proportion of MHC class II+ cells was larger among BM-derived (EGFP(+)/Iba-1(+)) than resident (EGFP(+)/Iba-1(+)) microglia. In the eyes with retinal detachment, EGFP(+)/F4/80(+) cells engrafted exclusively around the detached retina. CONCLUSIONS. In response to retinal damage, numerous BM-derived cells migrated to the retina from the ciliary body, optic nerve, and retinal vessels and differentiated into microglia. The higher rate of immunologic activation and the increased specificity to the damaged site appeared to be the characteristic features of BM-derived microglia.