Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only