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V. Vasireddy, W. W. Wrasidlo, J. A. Jamison, R. Ayyagari; Novel Analogue of Curcumin in Treating Retinal Degenerations. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3307.
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Defective protein trafficking followed by aggregation has been implicated in the pathology of several neurodegenerative diseases including retinal degeneration (RD). The purpose of the present study is to evaluate the therapeutic potential of a novel analogue of curcumin in treating RD due to protein trafficking defects.
A rat model with a missense mutation in the rhodopsin (P23H) gene was used to test the effect of a synthetic curcumin analogue,WW-II-88. The effect of WW-II-88 on aggregated mutant rhodopsin in transiently transfected cells was studied by immunocytochemistry, and confocal microscopy. The In vivo therapeutic potential of this analogue was tested by oral administration to P23H transgenic rats and compared with controls. Photoreceptor degeneration and the protective effect of the analogue was studied by evaluating retinal morphology at the end of treatment. Electroretinograms (ERG) were recorded from the anesthetized P23H-transgenic rats to determine retinal function after administering the WW-II-88. Localization of the rhodopsin in retina of curcumin analogue administered P23H-animals was evaluated by immunofluorescence analysis using specific retinal cell marker.
Mutant rhodopsin aggregates were found to be dissociated when treated with the analogue. The subcellular distribution pattern of this dissociated mutant rhodopsin was observed to be similar to the localization of wild type rhodopsin. Thickness of the outer nuclear layer and the ERG amplitudes showed significant improvement in treated rats compared to untreated controls. Immunohistochemical analysis of retina of treated rats demonstrated the translocation of rhodopsin to photoreceptor outer segments.
Dissociation of mutant rhodopsin aggregates, improved retinal morphology, physiology and translocation of rhodopsin to photoreceptor outer segments in P23H transgenic rat model in response to oral treatment with WW-II-88 demonstrated the therapeutic potential of this novel analogue in treating protein aggregation induced RD.
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