April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
The paradoxical role of CCL3 in acute and chronic retinal degeneration
Hideo Kohno; Tsutomu Sakai; Tadao Maeda; Eric Pearlman; Krzysztof Palczewski; Akiko Maeda
Author Affiliations & Notes
  • Hideo Kohno
    The department of Ophthalmology, The Jikei university school of medicine, Tokyo, Japan
    The department of Pharmacology, Case Western Reserve University, Cleveland, OH
  • Tsutomu Sakai
    The department of Ophthalmology, The Jikei university school of medicine, Tokyo, Japan
  • Tadao Maeda
    The department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH
  • Eric Pearlman
    The department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH
  • Krzysztof Palczewski
    The department of Pharmacology, Case Western Reserve University, Cleveland, OH
  • Akiko Maeda
    The department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH
    The department of Pharmacology, Case Western Reserve University, Cleveland, OH
  • Footnotes
    Commercial Relationships Hideo Kohno, None; Tsutomu Sakai, None; Tadao Maeda, None; Eric Pearlman, None; Krzysztof Palczewski, None; Akiko Maeda, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1254. doi:
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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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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 648 photoreceptors • 695 retinal degenerations: cell biology • 557 inflammation  
© 2014, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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