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A more recent version of this article appeared on May 1, 2009 Originally published In Press as doi:10.1194/jlr.M800170-JLR200 on November 20, 2008

Papers In Press, published online ahead of print March 16, 2009
J. Lipid Res., doi:10.1194/jlr.M800170-JLR200
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Submitted on April 7, 2008
Revised on November 5, 2008
Accepted on November 20, 2008

High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degeneration

Masaki Tanito, Richard S. Brush, Michael H. Elliott, Lea D. Wicker, Kimberly R. Henry, and Robert E. Anderson

Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501

Corresponding Author: tanito-oph{at}umin.ac.jp

The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [ fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology.


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[Abstract] [Full Text] [PDF]


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