PMID- 17284607
OWN - NLM
STAT- MEDLINE
DCOM- 20070517
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 7
DP  - 2007 Feb 13
TI  - Monocyte chemoattractant protein 1 mediates retinal detachment-induced 
      photoreceptor apoptosis.
PG  - 2425-30
AB  - Photoreceptor apoptosis is a major cause of visual loss in retinal detachment 
      (RD) and several other visual disorders, but the underlying mechanisms remain 
      elusive. Recently, increased expression of monocyte chemoattractant protein 1 
      (MCP-1) was reported in vitreous humor samples of patients with RD and diabetic 
      retinopathy as well as in the brain tissues of patients with neurodegenerative 
      diseases, including Alzheimer's disease and multiple sclerosis. Here we report 
      that MCP-1 plays a critical role in mediating photoreceptor apoptosis in an 
      experimental model of RD. RD led to increased MCP-1 expression in the Muller glia 
      and increased CD11b+ macrophage/microglia in the detached retina. An MCP-1 
      blocking antibody greatly reduced macrophage/microglia infiltration and 
      RD-induced photoreceptor apoptosis. Confirming these results, MCP-1 
      gene-deficient mice showed significantly reduced macrophage/microglia 
      infiltration after RD and very little photoreceptor apoptosis. In primary retinal 
      mixed cultures, MCP-1 was cytotoxic for recoverin+ photoreceptors, and this 
      toxicity was eliminated through immunodepleting macrophage/microglia from the 
      culture. In vivo, deletion of the gene encoding CD11b/CD18 nearly eliminated 
      macrophage/microglia infiltration to the retina after RD and the loss of 
      photoreceptors. Thus, MCP-1 expression and subsequent macrophage/microglia 
      infiltration and activation are critical for RD-induced photoreceptor apoptosis. 
      This pathway may be an important therapeutic target for preventing photoreceptor 
      apoptosis in RD and other CNS diseases that share a common etiology.
FAU - Nakazawa, Toru
AU  - Nakazawa T
AD  - Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of 
      Ophthalmology, and Children's Hospital, Harvard Medical School, Boston, MA 02114, 
      USA.
FAU - Hisatomi, Toshio
AU  - Hisatomi T
FAU - Nakazawa, Chifuyu
AU  - Nakazawa C
FAU - Noda, Kosuke
AU  - Noda K
FAU - Maruyama, Kazuichi
AU  - Maruyama K
FAU - She, Haicheng
AU  - She H
FAU - Matsubara, Akihisa
AU  - Matsubara A
FAU - Miyahara, Shinsuke
AU  - Miyahara S
FAU - Nakao, Shintaro
AU  - Nakao S
FAU - Yin, Yuqin
AU  - Yin Y
FAU - Benowitz, Larry
AU  - Benowitz L
FAU - Hafezi-Moghadam, Ali
AU  - Hafezi-Moghadam A
FAU - Miller, Joan W
AU  - Miller JW
LA  - eng
GR  - K08 AI050775/AI/NIAID NIH HHS/United States
GR  - EY014104/EY/NEI NIH HHS/United States
GR  - AI50775/AI/NIAID NIH HHS/United States
GR  - EY05690/EY/NEI NIH HHS/United States
GR  - R01 EY005690/EY/NEI NIH HHS/United States
GR  - P30 EY014104/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070206
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Chemokine CCL2)
RN  - 0 (Macrophage-1 Antigen)
SB  - IM
CIN - Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2033-4. PMID: 17284591
MH  - *Apoptosis
MH  - Cell Movement
MH  - *Chemokine CCL2
MH  - Coculture Techniques
MH  - Humans
MH  - Macrophage-1 Antigen/physiology
MH  - Macrophages/physiology
MH  - Microglia/physiology
MH  - Photoreceptor Cells/*pathology
MH  - Retinal Detachment/*etiology/*pathology
PMC - PMC1892947
COIS- The authors declare no conflict of interest.
EDAT- 2007/02/08 09:00
MHDA- 2007/05/18 09:00
PMCR- 2007/08/13
CRDT- 2007/02/08 09:00
PHST- 2007/02/08 09:00 [pubmed]
PHST- 2007/05/18 09:00 [medline]
PHST- 2007/02/08 09:00 [entrez]
PHST- 2007/08/13 00:00 [pmc-release]
AID - 0608167104 [pii]
AID - 4985 [pii]
AID - 10.1073/pnas.0608167104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2425-30. doi: 
      10.1073/pnas.0608167104. Epub 2007 Feb 6.