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Immunological protein expression in the eyes of Ccl2/Cx3cr1 deficient mice, a model of age‐related macular degeneration
Author(s) -
Ross Robert James,
Zhou Min,
Shen Defen,
Bojanowski Christine M,
Fariss Robert,
Tuo Jingsheng,
Chan ChiChao
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1130
Subject(s) - macular degeneration , cx3cr1 , retina , retinal , drusen , ccl2 , innate immune system , choroid , microglia , integrin alpha m , immunohistochemistry , pathology , biology , medicine , immune system , chemokine , immunology , ophthalmology , inflammation , neuroscience , chemokine receptor
The Ccl2/Cx3cr1 double knock‐out (DKO) mouse model consistently develops retinal degeneration with age‐related macular degeneration (AMD) features at a young age. Since there is strong evidence for an immunological role in the AMD pathogenesis, we determined ocular immune protein expression levels in DKO and age‐matched wild‐type (WT) mice. Immunohistochemistry revealed increased complement C3 expression in Bruch’s membrane, RPE, photoreceptors, choroidal capillaries, and particularly drusen of DKO mice relative to age‐matched WT. While the retina of the WT mice did not stain positive for macrophage (F4/80) or microglia (CD11b) markers, infiltrations were detected in the DKO retinal lesions. Autoantibody against retina was also detected in the DKO. The DKO had reduced macrophages in the choroid and reduced TLR4 in the RPE. Real‐time RT‐PCR revealed a significant increase in DKO Cx3cl1 and Ccl5 transcript relative to the WT. These results suggest innate immunity may play a critical role in DKO retinal degeneration. Moreover, since human AMD patients show similar immune profiles, the results support DKO as a suitable AMD model. Financial Support: NEI Intramural Program