Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis

Toru Nakazawa, Toshio Hisatomi, Chifuyu Nakazawa, Kosuke Noda, Kazuichi Maruyama, Haicheng She, Akihisa Matsubara, Shinsuke Miyahara, shintaro nakao, Yuqin Yin, Larry Benowitz, Ali Hafezi-Moghadam, Joan W. Miller

Research output: Contribution to journalArticle

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Abstract

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 Müller 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.

Original languageEnglish
Pages (from-to)2425-2430
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number7
DOIs
Publication statusPublished - Feb 13 2007

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Chemokine CCL2
Retinal Detachment
Microglia
Apoptosis
Macrophages
Retina
Alzheimer Disease
Recoverin
Vitreous Body
Blocking Antibodies
Central Nervous System Diseases
Vision Disorders
Gene Deletion
Diabetic Retinopathy
Neuroglia
Neurodegenerative Diseases
Multiple Sclerosis
Theoretical Models
Brain

All Science Journal Classification (ASJC) codes

  • General

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Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. / Nakazawa, Toru; Hisatomi, Toshio; Nakazawa, Chifuyu; Noda, Kosuke; Maruyama, Kazuichi; She, Haicheng; Matsubara, Akihisa; Miyahara, Shinsuke; nakao, shintaro; Yin, Yuqin; Benowitz, Larry; Hafezi-Moghadam, Ali; Miller, Joan W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 7, 13.02.2007, p. 2425-2430.

Research output: Contribution to journalArticle

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 2007, 'Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 7, pp. 2425-2430. https://doi.org/10.1073/pnas.0608167104
Nakazawa, Toru ; Hisatomi, Toshio ; Nakazawa, Chifuyu ; Noda, Kosuke ; Maruyama, Kazuichi ; She, Haicheng ; Matsubara, Akihisa ; Miyahara, Shinsuke ; nakao, shintaro ; Yin, Yuqin ; Benowitz, Larry ; Hafezi-Moghadam, Ali ; Miller, Joan W. / Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 7. pp. 2425-2430.
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AU - Noda, Kosuke

AU - Maruyama, Kazuichi

AU - She, Haicheng

AU - Matsubara, Akihisa

AU - Miyahara, Shinsuke

AU - nakao, shintaro

AU - Yin, Yuqin

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AU - Hafezi-Moghadam, Ali

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