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Cooperative phagocytes: resident microglia and bone marrow immigrants remove dead photoreceptors in retinal lesions


Joly, S; Francke, M; Ulbricht, E; Beck, S; Seeliger, M W; Hirrlinger, P; Hirrlinger, J; Lang, K S; Zinkernagel, M; Odermatt, B; Samardzija, M; Reichenbach, A; Grimm, C; Remé, C E (2009). Cooperative phagocytes: resident microglia and bone marrow immigrants remove dead photoreceptors in retinal lesions. American Journal of Pathology, 174(6):2310-2323.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Ophthalmology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:June 2009
Deposited On:03 Jun 2009 15:36
Last Modified:05 Apr 2016 13:14
Publisher:Elsevier
ISSN:0002-9440
Funders:Swiss National Science Foundation (3100A0-105793 and 3100A0-117760), Vontobel Foundation, German Research Council DFG grants Se 837/5-2, Se 837/6-1 and Se 837/7-1
Publisher DOI:https://doi.org/10.2353/ajpath.2009.090023
PubMed ID:19435787

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