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Hideo Kohno, Tsutomu Sakai, Tadao Maeda, Eric Pearlman, Krzysztof Palczewski, Akiko Maeda; The paradoxical role of CCL3 in acute and chronic retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1254.
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Accumulating evidence suggests that retinal inflammation plays a key or important role in visual impairment or loss seen in retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. However, the link between inflammation and retinal degeneration remains poorly defined. This work was conducted to better elucidate the role of chemokines in these retinal degenerative conditions.
Abca4-/-Rdh8-/- mice, which show acute (light induced) and chronic (age related) retinal degeneration due to impaired metabolism of all-trans-retinal, were employed in this study. First, RNA array analysis of chemokines in light exposed retina of Abca4-/-Rdh8-/- mice was performed. Second, the time course changes in chemokine expression were tested by qRT-PCR analysis. Finally, Ccl3-/-Abca4-/-Rdh8-/- mice were established by cross-breeding between Ccl3-/-and Abca4-/-Rdh8-/- mice, and retinal phenotype of acute and chronic retinal degeneration was compared.
The chemokine Ccl3 showed the highest increase among all tested chemokines by PCR-based RNA array analysis. Time coursed qRT-PCR results revealed rapid increase of macrophage inflammatory protein-1 (MIP-1) chemokines, including Ccl3 and Ccl4 compared to other chemokines. Ccl3-/-Abca4-/-Rdh8-/- mice showed exaggerated phenotype in acute light induced retinal degeneration compared to Abca4-/-Rdh8-/- mice. On the contrary, Ccl3-/-Abca4-/-Rdh8-/- mice showed attenuated retinal phenotype in age-related chronic degeneration compared to Abca4-/-Rdh8-/- mice.
Inflammatory chemokine Ccl3 displayed distinct effects in acute and chronic retinal degeneration in a mouse model of retinal degeneration. This result suggests the key role of CCL3 in mediating severity of inflammation and degenerative phenotypes in retinal disorders.
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