Deficiency of CC chemokine ligand 2 and decay-accelerating factor causes retinal degeneration in mice Journal Article

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Authors: Yu, M; Kang, K.; Bu, P; Bell, B. A.; Kaul, C.; Qiao, J. B.; Sturgill-Short, G.; Yu, X.; Tarchick, M. J.; Beight, C.; Zhang, S. X.; Peachey, N. S.
Article Title: Deficiency of CC chemokine ligand 2 and decay-accelerating factor causes retinal degeneration in mice
Abstract: CC chemokine ligand 2 (CCL2) recruits macrophages to reduce inflammatory responses. Decay-accelerating factor (DAF) is a membrane regulator of the classical and alternative pathways of complement activation. In view of the link between complement genes and retinal diseases, we evaluated the retinal phenotype of C57BL/6J mice and mice lacking Ccl2 and/or Daf1 at 12 months of age, using scanning laser ophthalmoscopic imaging, electroretinography (ERG), histology, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. In comparison to C57BL/6J mice, mutant mice had an increased number of autofluorescent foci, with the greatest number in the Ccl2-/-/Daf1-/- retina. ERG amplitudes in Ccl2-/-/Daf1-/-, Ccl2-/- and Daf1-/- mice were reduced, with the greatest reduction in Ccl2-/-/Daf1-/- mice. TUNEL-positive cells were not seen in C57BL/6J retina, but were prevalent in the outer and inner nuclear layers of Ccl2-/-Daf1-/- mice and were present at reduced density in Ccl2-/- or Daf1-/- mice. Cell loss was most pronounced in the outer and inner nuclear layers of Ccl2-/-/Daf1-/- mice. The levels of the endoplasmic reticulum chaperone GPR78 and transcription factor ATF4 were significantly increased in the Ccl2-/-/Daf1-/- retina. In comparison to the C57BL/6J retina, the phosphorylation of NF-kappaB p65, p38, ERK and JNK was significantly upregulated while SIRT1 was significantly downregulated in the Ccl2-/-/Daf1-/- retina. Our results suggest that loss of Ccl2 and Daf1 causes retinal neuronal death and degeneration which is related to increased endoplasmic reticulum stress, oxidative stress and inflammation.
Journal Title: Experimental eye research
Volume: 138
ISSN: 1096-0007; 0014-4835
Publisher: Elsevier Inc  
Date Published: 2015
Start Page: 126
End Page: 133
Language: ENG
DOI/URL:

S0014-4835(15)00169-4
Notes: LR: 20150811; CI: Copyright (c) 2015; JID: 0370707; OTO: NOTNLM; 2015/03/16 [received]; 2015/05/22 [revised]; 2015/05/25 [accepted]; aheadofprint
LUC Authors
  1. Ping Bu
    11 Bu
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