RGD Reference Report - Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. - Rat Genome Database

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Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis.

Authors: Nakazawa, T  Hisatomi, T  Nakazawa, C  Noda, K  Maruyama, K  She, H  Matsubara, A  Miyahara, S  Nakao, S  Yin, Y  Benowitz, L  Hafezi-Moghadam, A  Miller, JW 
Citation: Nakazawa T, etal., Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2425-30. Epub 2007 Feb 6.
RGD ID: 8548846
Pubmed: PMID:17284607   (View Abstract at PubMed)
PMCID: PMC1892947   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0608167104   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinal detachment  ISOCcl2 (Mus musculus)8548846; 8548846 RGD 
retinal detachment  IMP 8548846 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information