Published online before print May 12, 2009

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Copyright © 2009 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2009.090023

Accepted for publication March 5, 2009.

Article

Cooperative Phagocytes: Resident Microglia and Bone Marrow Immigrants Remove Dead Photoreceptors in Retinal Lesions

Sandrine Joly^*@, Mike Francke, Elke Ulbricht, Susanne Beck, Matthias Seeliger, Petra Hirrlinger, Johannes Hirrlinger, Karl S. Lang^¶, Martin Zinkernagel^||, Bernhard Odermatt^**, Marijana Samardzija^*, Andreas Reichenbach, Christian Grimm^*, and Charlotte E. Remé^*@

From the Laboratory for Retinal Cell Biology,* Department of Ophthalmology, University of Zurich, Zurich, Switzerland; the Paul-Flechsig-Institute for Brain Research, University of Leipzig, Leipzig, Germany; the Ocular Neurodegeneration Research Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany; the Interdisciplinary Centre for Clinical Research, N05-Neural Plasticity, Leipzig, Germany; the Institutes of Experimental Immunology^¶ and Pathology,** University Hospital of Zurich, Zurich, Switzerland; and the Research Department,^|| Kantonal Hospital of St. Gallen, Gallen, Switzerland

^@ To whom correspondence should be addressed. E-mail: sandrine.joly{at}usz.ch.

	Abstract

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.