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Atsushi Otani, Congrong Guo, Akio Oishi, Nagahisa Yoshimura; Knockout Of Ccr2 Promotes Photoreceptor Survival In A Model Of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5631.
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© ARVO (1962-2015); The Authors (2016-present)
Chemokines are immune signalling cytokines that control inflammation by functioning as chemoattractants that recruit inflammatory cells into the sites of inflammation. In the present study the role of a CC chemokine, monocyte chemoattractant protein-1 (MCP-1) was investigated in the pathology of retinitis pigmentosa (RP), an inherited retinal degenerative disease.
The expression pattern of MCP-1 and other chemokines were examined in rd10 mice, dark-reared mice and ccr2-/- rd10 mice (generated by CCR2 knockout mice and rd10 mice). Retinal morphology was analyzed by both live imaging (using OCT) and histological analysis and retinal function was investigated by electroretinogram (ERG) .
The MCP-1 level in rd10 mice was more than 30 times than that of control mice at P24 and remained significantly higher than in control mice through at least P36. The expression of other CC chemokine RANTES was similar to that of MCP-1, however the peak of CXC chemokine SDF-1 expression shifted to a later time point. The dark-reared mice experiment revealed that the expression of chemokines increased in parallel with the progression of degeneration in rd10 retina. ccr2 knockout rescued photoreceptor cells both morphologically and functionally. ccr2 knockout diminished the increased MCP-1 but not RANTES or SDF-1 mRNA expression in rd10 retina.
Our results demonstrate that MCP-1 and CCR2-positive cells may negatively impact photoreceptor survival. The contribution of each chemokine to the degeneration process may be different.
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