May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Protective Activity of Myricetin-Like Flavones and Cyanidins in Light-Induced Retinal Damage
Author Affiliations & Notes
  • L. Zhu
    Acucela Inc., Bothell, Washington
  • D. Leung
    Acucela Inc., Bothell, Washington
  • L. Lindlief
    Acucela Inc., Bothell, Washington
  • M. Kamat
    Acucela Inc., Bothell, Washington
  • R. Tzekov
    Acucela Inc., Bothell, Washington
  • R. Kubota
    Acucela Inc., Bothell, Washington
  • A. Fawzi
    Acucela Inc., Bothell, Washington
  • Footnotes
    Commercial Relationships  L. Zhu, Acucela Inc., E; D. Leung, Acucela Inc., E; L. Lindlief, Acucela Inc., E; M. Kamat, Acucela Inc., E; R. Tzekov, Acucela Inc., E; R. Kubota, Acucela Inc., E; A. Fawzi, Acucela Inc., E.
  • Footnotes
    Support  NIH/NEI SBIR Grant 1R43EY018266-01A1
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4415. doi:
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      L. Zhu, D. Leung, L. Lindlief, M. Kamat, R. Tzekov, R. Kubota, A. Fawzi; Protective Activity of Myricetin-Like Flavones and Cyanidins in Light-Induced Retinal Damage. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4415.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : We investigated the protective activity of flavone and cyanidin subfamilies of flavonoids against light and A2E stress in cultured retinal cells and against light damage in vivo.

Methods: : Selected flavones (21) and cyanidins (3) were tested at 12µM in bovine primary retinal cell cultures against actinic blue light and in ARPE-19 cells against blue light and A2E stress. To evaluate the protective activity of these compounds against light damage in vivo, BALB/c mice were dosed with selected flavonoids (50 mg/kg, i.p.) before exposure to 5000 lux white light. Retinal cell apoptosis was evaluated by measuring nucleosome release. Two weeks after light exposure, retinal morphology of flavone- or cyanidin-treated mice was evaluated by measuring retinal outer segment thickness with light microscopy.

Results: : Most of the tested flavones or cyanidins were protective in ARPE-19 cells against A2E plus light stress. Among 21 tested flavones, 7,3’,4’,5’-tetrahydroxyflavone and 5,7,3’,4’,5’-pentahydroxyflavone are the only two that showed protective activity against blue light stress in primary retinal cell cultures. Meanwhile, all of the three tested cyanidins showed protective activity against blue light in vitro. Except for pelargonidin, all other four protective compounds (in-vitro) showed significant protection against light-induced retinal damage in mice. At the dose of 50 mg/kg (i.p.), 5,7,3’,4’,5’-pentahydroxyflavone, cyanidin and definidin showed greater than 95% protection compared to control.

Conclusions: : The protective effect of tested flavones and cyanidins against light-induced damage increases within each subfamily, both in vitro and in vivo, as the hydroxyl group substitution on the B ring increases. Interestingly, the order of protection strength of the tested flavonoids against light damage did not correlate with the reported order of antioxidant capacity, suggesting alternative protective mechanisms.

Keywords: apoptosis/cell death • retinal degenerations: cell biology • antioxidants 
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