May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Comparison of the Susceptibility of Fat-1 and Wild Type Mice Fed an N-3 Polyunsaturated Fatty Acid Deficient Diet to Light-Induced Retinal Degeneration
Author Affiliations & Notes
  • M. Tanito
    Ophthalmology, Shimane University Faculty of Medicine, Izumo, Japan
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  • M. H. Elliott
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma
  • R. S. Brush
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma
  • L. D. Wicker
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma
  • K. R. Henry
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma
  • R. E. Anderson
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
    Dean A. McGee Eye Institute, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  M. Tanito, None; M.H. Elliott, None; R.S. Brush, None; L.D. Wicker, None; K.R. Henry, None; R.E. Anderson, None.
  • Footnotes
    Support  NEI (EY04149, EY00871, and EY12190); NCRR (RR17703); RPB; FFB; and JSPS
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5924. doi:
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      M. Tanito, M. H. Elliott, R. S. Brush, L. D. Wicker, K. R. Henry, R. E. Anderson; Comparison of the Susceptibility of Fat-1 and Wild Type Mice Fed an N-3 Polyunsaturated Fatty Acid Deficient Diet to Light-Induced Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5924.

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

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Abstract

Purpose: : The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 polyunsaturated fatty acids (PUFA) to n-3 PUFA. We tested if dietary deprivation of n-3 PUFA may affect the susceptibility of albino mice to light-induced retinal degeneration.

Methods: : Mice carrying the fat-1 transgene and wild type controls were fed a 10% safflower oil diet, which is deficient in n-3 and enriched in n-6 PUFA (fat-1-SFO and wt-SFO, resp.), and exposed to 3000 lux fluorescent light for 24 h. Retinal damage was estimated by electroretinogram (ERG) recording, outer nuclear layer (ONL) thickness measurement, TUNEL staining of retinal sections, and Western dotblot analyses for retinal protein modifications by 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE). The latter are end-products of n-3 and n-6 PUFA oxidation, resp. Fatty acid profiles of rod outer segments (ROS) were determined by gas-liquid chromatography.

Results: : In ROS, n-6/n-3 ratios were significantly lower in fat-1-SFO compared to wt-SFO. Compared to light-exposed wt-SFO, fat-1-SFO mice had (1) reduced thickness of the ONL thickness; (2) lower a- and b-wave amplitudes of the ERG, and (3) greater number of apoptotic photoreceptor cells. With damaging light exposure, modification of retinal proteins by 4-HHE was increased in fat-1-SFO compared to wt-SFO and to unexposed animals. However, modification of retinal proteins by 4-HNE was increased in both light-exposed groups compared to unexposed animals.

Conclusions: : There is positive correlation between the levels of n-3 PUFA, the amount of n-3 PUFA peroxidation, and the vulnerability of rod photoreceptors to photo-oxidative stress.

Keywords: oxidation/oxidative or free radical damage • retinal degenerations: cell biology • lipids 
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