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T. Nakazawa, A. Mastubara, K. Noda, T. Hisatomi, H. She, S. Miyahara, D. Skondra, A. Hafezi–Moghadam, J.W. Miller; Critical Role of MCP–1 in Photoreceptor Degeneration After Retinal Detachment in Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4563.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate whether monocyte chemoattractant protein–1 (MCP–1) plays a role in the photoreceptor degeneration that follows retinal detachment (RD).
MCP–1 deficient (MCP–1–/–) and age–matched wild–type (WT) mice on the C57BL/6 genetic background were used in this study. RD was induced by subretinal injection of sodium hyaluronate. The expression of mRNA for MCP–1 was assessed by quantitative real time polymerase chain reaction (QPCR) at 72 h after RD. MCP–1 expression was determined by immunohistochemistry (IHC) and ELISA. Photoreceptor cell death was determined using a TdT–dUTP terminal nick–end labeling (TUNEL) assay. The number of TUNEL–positive cells and the thickness of the outer nuclear layer (ONL) 7 days after RD were compared in MCP–1–/– and WT mice. Acute blockade of MCP–1 was studied using a neutralizing Fab antibody (11K2, 0.5ug) injected subretinally in WT mice at the time of RD–induction and photoreceptor degeneration was quantified by TUNEL assay.
At day 3 after RD, significant increases were detected in mRNA (p=0.001, n=6) and protein levels (p=0.0018, n=6) for MCP–1 in the retinas of WT mice. IHC revealed that MCP–1 was increased in the Muller cells. Compared to WT, MCP–1–/– mice showed significantly (P<0.0001, n=10) less photoreceptor degeneration as determined by TUNEL assay. At day 7 after RD, the ONL thickness was decreased by 64.9% in WT mice, while MCP–1 –/– mice showed significantly less decrease of the ONL thickness (95.1%, P<0.0001, n=10). Subretinal administration of blocking MCP–1 Fab antibody significantly suppressed the number of TUNEL–positive cells in the ONL at 72 h after RD (P<0.0001, n=10).
Lack of MCP–1 or its acute blockade with neutralizing Fab fragments protects against RD–induced photoreceptor degeneration in murine models. Our data suggest that MCP–1 plays a role in retinal degeneration associated with retinal detachment. Interference with MCP–1 may provide a new therapeutic approach for photoreceptor protection.
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