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

Abstract

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.

• Authors: Jingsheng Tuo, Robert J Ross, Alexandra A Herzlich, Defen Shen, Xiaoyan Ding, Min Zhou, Steven L Coon, Nahed Hussein, Norman Salem Jr, Chi-Chao Chan
• Journal: The American journal of pathology (Am J Pathol) Vol. 175 Issue 2 Pg. 799-807 (Aug 2009) ISSN: 1525-2191 [Electronic] United States
• PMID: 19608872 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• 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

Topics

• 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, prevention & control, therapy)
• Mice
• Mice, Mutant Strains
• Pyridinium Compounds (metabolism)
• Receptors, Chemokine (genetics)
• Retinal Pigment Epithelium (drug effects, metabolism, pathology)
• Retinoids (metabolism)
• Transcription, Genetic
• Tumor Necrosis Factor-alpha (genetics)