April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Polyphenols and Phytoalexins in Treating Retinal Degenerations
Author Affiliations & Notes
  • V. Vasireddy
    Ophthalmology, University of California San Diego, La Jolla, California
  • B. Geereddy
    National Institute of Nutrition, Hyderabad, India
  • R. Kadam
    Pharmaceutical Sciences & Ophthalmology, University of Colorado Denver, Arora, Colorado
  • W. Wrasidlo
    University of California San Diego Moores Cancer Center, La Jolla, California
  • U. B. Kompella
    Pharmaceutical Sciences & Ophthalmology, University of Colorado Denver, Arora, Colorado
  • R. Ayyagari
    Ophthalmology, University of California San Diego, La Jolla, California
  • Footnotes
    Commercial Relationships  V. Vasireddy, None; B. Geereddy, None; R. Kadam, None; W. Wrasidlo, None; U.B. Kompella, None; R. Ayyagari, None.
  • Footnotes
    Support  EY13198
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 672. doi:
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      V. Vasireddy, B. Geereddy, R. Kadam, W. Wrasidlo, U. B. Kompella, R. Ayyagari; Polyphenols and Phytoalexins in Treating Retinal Degenerations. Invest. Ophthalmol. Vis. Sci. 2009;50(13):672.

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

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Purpose: : Altered protein trafficking due to abnormal protein aggregation has been implicated in the pathology of retinal degenerations (RD). Pharmacological agents with anti-protein aggregating properties may aid in treating this class of RD. The purpose of the present study is to evaluate the potential beneficiary effects of polyphenols/phytoalexins and their derivatives in treating RD.

Methods: : Models of RD due to a 5-bp deletion mutation in the gene Elongation of very long chain fatty acids-4 (ELOVL4) and a missense mutation in rhodopsin (P23H) were used to test the effect of polyphenols/phytoalexins and their derivatives. The bioavailability of these compounds after oral administration was evaluated by LC-MS/MS analysis of the eyes and brain tissues. The effect of these compounds on protein aggregation in transiently transfected cells was studied by immunocytochemistry, confocal microscopy, western blot analysis and qRT-PCR. The in vivo effect of these compounds was tested by oral administration to animal models with RD followed by histological evaluation of the retina.

Results: : Bioavailability assays revealed the presence of 8-20 ng of polyphenols/ gm tissue and 1-3 ng of phytoalexins/gm tissue following administration of an oral dose 100mg/ kg body weight . Dissociation of mutant ELOVL4/P23H RHO aggregates, increased solubility of these proteins; and a decrease in the expression of genes specific to unfolded protein response was observed in cells treated with polyphenols/phytoalexins and their derivatives . In addition, the localization of mutant proteins in these cells was similar to the distribution pattern of wild type protein. Retinal morphology of animals administered with polyphenols/phytoalexins showed improvement.

Conclusions: : Retinal bioavailability,dissociation of protein aggregates, and improved retinal morphology in RD models in response to treatment indicates the therapeutic potential of polyphenols/phytoalexins in treating RD due to protein aggregation.

Keywords: degenerations/dystrophies • retinal degenerations: cell biology • antioxidants 

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