Cooperative phagocytes: resident microglia and bone marrow immigrants remove dead photoreceptors in retinal lesions.
Phagocytosis is essential for the removal of photoreceptor debris following retinal injury. We used two mouse models, mice injected with green fluorescent protein-labeled bone marrow cells or green fluorescent protein-labeled microglia, to study the origin and activation patterns of phagocytic cells after acute blue light-induced retinal lesions. We show that following injury, blood-borne macrophages enter the eye via the optic nerve and ciliary body and soon migrate into the injured retinal area. Resident microglia are also activated rapidly throughout the entire retina and adopt macrophage characteristics only in the injured region. Both blood-borne- and microglia-derived macrophages were involved in the phagocytosis of dead photoreceptors. No obvious breakdown of the blood-retinal barrier was observed. Ccl4, Ccl12, Tgfb1, Csf1, and Tnf were differentially expressed in both the isolated retina and the eyecup of wild-type mice. Debris-laden macrophages appeared to leave the retina into the general circulation, suggesting their potential to become antigen-presenting cells. These experiments provide evidence that both local and immigrant macrophages remove apoptotic photoreceptors and cell debris in the injured retina.
Joly
Sandrine
S
Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Frauenklinikstr. 24, 8091 Zurich, Switzerland.
Francke
Mike
M
Ulbricht
Elke
E
Beck
Susanne
S
Seeliger
Matthias
M
Hirrlinger
Petra
P
Hirrlinger
Johannes
J
Lang
Karl S
KS
Zinkernagel
Martin
M
Odermatt
Bernhard
B
Samardzija
Marijana
M
Reichenbach
Andreas
A
Grimm
Christian
C
Remé
Charlotte E
CE
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D049452:Green Fluorescent Proteins; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000276:immunology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000276:immunology; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D012160:Retina / Q000166:cytology* / Q000276:immunology* / Q000293:injuries; D020133:Reverse Transcriptase Polymerase Chain Reaction
D049452:Green Fluorescent Proteins