PMID- 23022404
OWN - NLM
STAT- MEDLINE
DCOM- 20130125
LR  - 20220309
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 104
DP  - 2012 Nov
TI  - Knockout of ccr2 alleviates photoreceptor cell death in a model of retinitis 
      pigmentosa.
PG  - 39-47
LID - S0014-4835(12)00271-0 [pii]
LID - 10.1016/j.exer.2012.08.013 [doi]
AB  - Neuroinflammation involving CC chemokines such as monocyte chemoattractant 
      protein-1 (MCP-1) has been demonstrated in the pathological process of retinitis 
      pigmentosa (RP), an inherited degenerative retinal disease. However, the 
      mechanism of MCP-1 and its receptor CCR2 involvement in the disease remains 
      unclear. To investigate the role of MCP1/CCR2 in RP pathogenesis, ccr2 mutant RP 
      mice (ccr2(-/-) rd10) were created and analyzed. The expression of MCP-1, RANTES, 
      stromal cell-derived factor (SDF-1), and tumor necrosis factor-alpha (TNF-alpha) in the 
      retinas of wild-type, rd10, and ccr2(-/-) rd10 mice was analyzed using 
      quantitative RT-PCR. Photoreceptor apoptosis (TUNEL staining) and the number of 
      microglia (positive for the F4/80 antibody) in the retina were examined. Retinal 
      function was assessed using electroretinograms, and the structure of the whole 
      retina was analyzed from images obtained using optical coherence tomography (OCT) 
      and by histological examination. The expression levels of MCP-1, RANTES, and 
      SDF-1 increased with time in the rd10 mice but not in the wild-type mice. Rearing 
      the mice in the dark prevented degeneration and resulted in thicker photoreceptor 
      layers at each time point. In those mice, the peaks of chemokine expression 
      shifted to a later time with degeneration, suggesting that the expression of 
      these chemokines was induced during the progression of degeneration. Although the 
      difference was not so obvious, the retina in the ccr2(-/-) rd10 mice was 
      consistently and significantly thicker than that in the rd10 (ccr2(+/+) rd10) 
      mice at all time points. Rhodopsin gene expression was also higher in the 
      ccr2(-/-) rd10 mice than in rd10 (ccr2(+/+) rd10) mice, suggesting photoreceptor 
      survival in the former. Retinal function was also better preserved in the 
      ccr2(-/-) rd10 mice than in the rd10 mice. The number of microglia in the retinas 
      of the ccr2(-/-) rd10 mice was significantly lower than that in the retinas of 
      the rd10 mice. Interestingly, the MCP-1 induction that was observed in the 
      retinas of the rd10 mice was diminished in the retinas of the ccr2(-/-) rd10 
      mice. Our results suggest that the MCP-1/CCR2 system plays a role in retinal 
      degeneration in rd mouse retinas. Retinal MCP-1 expression in the rd mouse retina 
      may be partially controlled by ccr2-positive circulating cells.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Guo, Congrong
AU  - Guo C
AD  - Department of Ophthalmology, Kyoto University Graduate School of Medicine, 
      54-Kawaharacho, Shogoin, Kyoto 606-8507, Japan.
FAU - Otani, Atsushi
AU  - Otani A
FAU - Oishi, Akio
AU  - Oishi A
FAU - Kojima, Hiroshi
AU  - Kojima H
FAU - Makiyama, Yukiko
AU  - Makiyama Y
FAU - Nakagawa, Satoko
AU  - Nakagawa S
FAU - Yoshimura, Nagahisa
AU  - Yoshimura N
LA  - eng
PT  - Journal Article
DEP - 20120926
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccl5 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Biomarkers/metabolism
MH  - Cell Survival
MH  - Chemokine CCL2/physiology
MH  - Chemokine CCL5/metabolism
MH  - Chemokine CXCL12/metabolism
MH  - Dark Adaptation
MH  - *Disease Models, Animal
MH  - Electroretinography
MH  - Fluorescent Antibody Technique, Indirect
MH  - Genotyping Techniques
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Photoreceptor Cells, Vertebrate/*physiology
MH  - RNA, Messenger/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, CCR2/*physiology
MH  - Retinitis Pigmentosa/genetics/metabolism/*prevention & control
MH  - Tomography, Optical Coherence
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2012/10/02 06:00
MHDA- 2013/01/26 06:00
CRDT- 2012/10/02 06:00
PHST- 2012/02/27 00:00 [received]
PHST- 2012/07/23 00:00 [revised]
PHST- 2012/08/31 00:00 [accepted]
PHST- 2012/10/02 06:00 [entrez]
PHST- 2012/10/02 06:00 [pubmed]
PHST- 2013/01/26 06:00 [medline]
AID - S0014-4835(12)00271-0 [pii]
AID - 10.1016/j.exer.2012.08.013 [doi]
PST - ppublish
SO  - Exp Eye Res. 2012 Nov;104:39-47. doi: 10.1016/j.exer.2012.08.013. Epub 2012 Sep 
      26.