May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Apoptosis of Cultured Rat Retinal Cells and Human Retinal Pigment Epithelial Cells Induced by Clioquinol
Author Affiliations & Notes
  • D.–S. Kim
    Department of Ophthalmology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
  • M. Yoo
    Creative Research Initiative Center for the Study of CNS Zinc, Seoul, Republic of Korea
  • J.–Y. Koh
    Creative Research Initiative Center for the Study of CNS Zinc, Seoul, Republic of Korea
  • Y. Yoon
    Department of Ophthalmology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
  • Footnotes
    Commercial Relationships  D. Kim, None; M. Yoo, None; J. Koh, None; Y. Yoon, None.
  • Footnotes
    Support  Korean Ministry of Health and Welfare Grant 02–PJ1–PG1–CH02–0003
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 5317. doi:
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      D.–S. Kim, M. Yoo, J.–Y. Koh, Y. Yoon; Apoptosis of Cultured Rat Retinal Cells and Human Retinal Pigment Epithelial Cells Induced by Clioquinol . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5317.

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Abstract

Abstract: : Purpose: Clioquinol is a metal chelator/antibiotic, which is currently being considered as potential drug in Alzheimer's disease. Since clioquinol was implicated in subacute myelo–optic neuropathy (SMON), we sought to evaluate the cytotoxic effect of clioquinol on rat retinal cells and human retinal pigment epithelial cells. Methods: Rat retinal cell culture and human retinal pigment epithelial cell culture were used. Cell degeneration was examined under light microscopy, and quantified by cell counting and lactase dehydrogenase (LDH) release assay. Additionally, TdT–mediated dUTP nick end labeling (TUNEL) staining, Western blots for caspase activation, electromicroscopy and confocal microscopy were performed. Results: Exposure to 1 ng/ml – 10µg/ml clioquinol for 24 and 48 hours induced cell death in a concentration–dependent manner. At 10 µg/ml, clioqionol induced more than 50 % of cell death. Indicating that clioquinol–induced cell death occurs mainly by apoptosis, it was accompanied by features characteristic of apoptosis such as vacuolar changes, membrane blebbing, chromatin condensation, nuclear fragmentation, and caspase–3 activation. In addition, as observed in apoptosis of several other cell types, cycloheximide as well as caspase inhibitors protected against clioquinol–induced cell death. Conclusions: The present results suggest that high levels of clioquinol is directly toxic to retinal and RPE cells, triggering classical apoptois cascade. This toxic mechanism may underlie SMON, a known complication of clioquinol treatment.

Keywords: apoptosis/cell death • drug toxicity/drug effects • retinal culture 
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