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Supranormal electroretinogram in fat-1 mice with retinas enriched in docosahexaenoic acid and n-3 very long chain fatty acids (C24-C36).
Invest Ophthalmol Vis Sci 2009; 50(9):4394-401IO

Abstract

PURPOSE

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.

Authors+Show Affiliations

Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. suh@ms.umanitoba.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19264893

Citation

Suh, Miyoung, et al. "Supranormal Electroretinogram in Fat-1 Mice With Retinas Enriched in Docosahexaenoic Acid and N-3 Very Long Chain Fatty Acids (C24-C36)." Investigative Ophthalmology & Visual Science, vol. 50, no. 9, 2009, pp. 4394-401.
Suh M, Sauvé Y, Merrells KJ, et al. Supranormal electroretinogram in fat-1 mice with retinas enriched in docosahexaenoic acid and n-3 very long chain fatty acids (C24-C36). Invest Ophthalmol Vis Sci. 2009;50(9):4394-401.
Suh, M., Sauvé, Y., Merrells, K. J., Kang, J. X., & Ma, D. W. (2009). Supranormal electroretinogram in fat-1 mice with retinas enriched in docosahexaenoic acid and n-3 very long chain fatty acids (C24-C36). Investigative Ophthalmology & Visual Science, 50(9), pp. 4394-401. doi:10.1167/iovs.08-2565.
Suh M, et al. Supranormal Electroretinogram in Fat-1 Mice With Retinas Enriched in Docosahexaenoic Acid and N-3 Very Long Chain Fatty Acids (C24-C36). Invest Ophthalmol Vis Sci. 2009;50(9):4394-401. PubMed PMID: 19264893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Supranormal electroretinogram in fat-1 mice with retinas enriched in docosahexaenoic acid and n-3 very long chain fatty acids (C24-C36). AU - Suh,Miyoung, AU - Sauvé,Yves, AU - Merrells,Krystal J, AU - Kang,Jing X, AU - Ma,David W L, Y1 - 2009/03/05/ PY - 2009/3/7/entrez PY - 2009/3/7/pubmed PY - 2009/9/19/medline SP - 4394 EP - 401 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 50 IS - 9 N2 - PURPOSE: 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. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/19264893/Supranormal_electroretinogram_in_fat_1_mice_with_retinas_enriched_in_docosahexaenoic_acid_and_n_3_very_long_chain_fatty_acids__C24_C36__ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.08-2565 DB - PRIME DP - Unbound Medicine ER -