Long-chain and very long-chain polyunsaturated fatty acids in ocular aging and age-related macular degeneration

  1. Paul S. Bernstein1,*
  1. *Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132
  2. Scientific Instruments Division, ThermoFisher Scientific, San Jose, CA 95134

    Abstract

    Retinal long-chain PUFAs (LC-PUFAs, C12-C22) play important roles in normal human retinal function and visual development, and some epidemiological studies of LC-PUFA intake suggest a protective role against the incidence of advanced age-related macular degeneration (AMD). On the other hand, retinal very long-chain PUFAs (VLC-PUFAs, Cn>22) have received much less attention since their identification decades ago, due to their minor abundance and more difficult assays, but recent discoveries that defects in VLC-PUFA synthetic enzymes are associated with rare forms of inherited macular degenerations have refocused attention on their potential roles in retinal health and disease. We thus developed improved GC-MS methods to detect LC-PUFAs and VLC-PUFAs, and we then applied them to the study of their changes in ocular aging and AMD. With ocular aging, some VLC-PUFAs in retina and retinal pigment epithelium (RPE)/choroid peaked in middle age. Compared with age-matched normal donors, docosahexaenoic acid, adrenic acid, and some VLC-PUFAs in AMD retina and RPE/choroid were significantly decreased, whereas the ratio of n-6/n-3 PUFAs was significantly increased. All these findings suggest that deficiency of LC-PUFAs and VLC-PUFAs, and/or an imbalance of n-6/n-3 PUFAs, may be involved in AMD pathology.

    Footnotes

    • 1 To whom correspondence should be addressed. e-mail: paul.bernstein{at}hsc.utah.edu

    • Abbreviations:
      AA
      arachidonic acid
      AMD
      age-related macular degeneration
      CEP
      carboxyethyl pyrrole
      DHA
      docosahexaenoic acid
      EFA
      essential FA
      EI
      electron ionization
      EPA
      eicosapentaenoic acid
      FAME
      fatty acid methyl ester
      LA
      linoleic acid
      LC-FA
      long-chain FA
      LCI
      liquid chemical ionization
      LC-PUFA
      long-chain PUFA
      NIST
      National Institute of Standards and Technology
      OA
      oleic acid
      PA
      palmitic acid
      RPE
      retinal pigment epithelium
      SA
      stearic acid
      SIM
      selected ion monitoring
      VLC-PUFA
      very long-chain PUFA

    • This work was supported by grants from the Steinbach Foundation, the Macula Vision Research Foundation, and a departmental grant from Research to Prevent Blindness.

    • Received April 18, 2010.
    • Revision received August 5, 2010.
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    1. The Journal of Lipid Research, 51, 3217-3229.
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