A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration

Am J Pathol. 2009 Aug;175(2):799-807. doi: 10.2353/ajpath.2009.090089. Epub 2009 Jul 16.


Age-related macular degeneration (AMD) is one of the leading cause of blindness among the elderly; however, current therapy options are limited. Epidemiological studies have shown that a diet that is high in omega-3 polyunsaturated (n-3) fatty acids can slow disease progression in patients with advanced AMD. In this study, we evaluated the effect of such a diet on the retinas of Ccl2(-/-)/Cx3cr1(-/-) mice, a model that develops AMD-like retinal lesions that include focal deep retinal lesions, abnormal retinal pigment epithelium, photoreceptor degeneration, and A2E accumulation. Ccl2(-/-)/Cx3cr1(-/-) mice that ingested a high n-3 fatty acid diet showed a slower progression of retinal lesions compared with the low n-3 fatty acids group. Some mice that were given high levels of n-3 fatty acids had lesion reversion. We found a shunted arachidonic acid metabolism that resulted in decreased pro-inflammatory derivatives (prostaglandin E(2) and leukotriene B(4)) and an increased anti-inflammatory derivative (prostaglandin D(2)). We also measured lower ocular TNF-alpha and IL-6 transcript levels in the mice fed a diet of high n-3 fatty acids. Our findings in these mice are in line with human studies of AMD risk reduction by long-chain n-3 fatty acids. This murine model provides a useful tool to evaluate therapies that might delay the development of AMD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • CX3C Chemokine Receptor 1
  • Chemokine CCL2 / genetics
  • Diet
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / administration & dosage*
  • Interleukin-6 / genetics
  • Macular Degeneration / pathology
  • Macular Degeneration / prevention & control
  • Macular Degeneration / therapy*
  • Mice
  • Mice, Mutant Strains
  • Pyridinium Compounds / metabolism
  • Receptors, Chemokine / genetics
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology
  • Retinoids / metabolism
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / genetics


  • A2-E (N-retinylidene-N-retinylethanolamine)
  • CX3C Chemokine Receptor 1
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Cx3cr1 protein, mouse
  • Fatty Acids, Omega-3
  • Interleukin-6
  • Pyridinium Compounds
  • Receptors, Chemokine
  • Retinoids
  • Tumor Necrosis Factor-alpha
  • Arachidonic Acid