Supranormal electroretinogram in fat-1 mice with retinas enriched in docosahexaenoic acid and n-3 very long chain fatty acids (C24-C36).
OBJECTIVE
Fat-1 mice can convert n-6 to n-3 fatty acids endogenously, resulting in the accumulation of n-3 fatty acids in major tissues. This was a study of how this conversion affects the major fatty acid found in retina, n-3 docosahexaenoic acid (DHA), the very long chain fatty acids (VLCFA, C24-C36), and retinal function.


METHODS
Both wild-type (WT) and fat-1 mice were fed a modified AIN-93G diet containing 10% safflower oil, high in 18:2n-6. Fatty acid composition of individual phospholipids was analyzed in total lipid extracts from whole eyes excluding the lens. Retinal function and levels of proteins involved in cellular stress were assessed with full field electroretinogram (ERG) recordings and immunohistochemistry, respectively.


RESULTS
Compared with WT mice, DHA levels in fat-1 mice increased two to five times in all phospholipid classes, whereas n-6 fatty acid levels decreased. Levels of C32 and C34 n-3 pentaenoic and hexaenoic VLCFA in phosphatidylcholine increased whereas n-6 VLCFAs were depleted. Scotopic and photopic ERGs showed unusually high amplitudes for both a- and b-waves and lower thresholds in fat-1 mice. Glial fibrillary acidic protein (GFAP) and carboxyethylpyrrole (CEP, protein adducts produced from DHA oxidation) were respectively increased in Müller cells and photoreceptors of fat-1 mice.


CONCLUSIONS
Highly enriched DHA and n-3 VLCFA in the retina lead to supernormal scotopic and photopic ERGs and increases in Müller cell reactivity and oxidative stress in photoreceptors. The regulation of n-3 fatty acids levels and of the n-6/n-3 fatty acid ratio are essential in preserving retinal integrity.
Suh
Miyoung
M
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. suh@ms.umanitoba.ca
Sauvé
Yves
Y
Merrells
Krystal J
KJ
Kang
Jing X
JX
Ma
David W L
DW
D000818:Animals; D015153:Blotting, Western; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D004032:Diet; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D004596:Electroretinography; D044943:Fatty Acid Desaturases / Q000502:physiology*; D005227:Fatty Acids / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012160:Retina / Q000502:physiology*; D012450:Safflower Oil / Q000008:administration & dosage
D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005904:Glial Fibrillary Acidic Protein; D010743:Phospholipids; C466741:fat-1 protein, C elegans; D004281:Docosahexaenoic Acids; D012450:Safflower Oil; D044943:Fatty Acid Desaturases