title: 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.affiliation: 10/10N103, NIH/NEI, 10 Center Dr., Bethesda, MD 20892-1857, USA.
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Tuo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ross
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Herzlich
authors.forename: Defen
authors.initials: D
authors.lastname: Shen
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ding
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Steven L
authors.initials: SL
authors.lastname: Coon
authors.forename: Nahed
authors.initials: N
authors.lastname: Hussein
authors.forename: Norman
authors.initials: N
authors.lastname: Salem
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2 / Q000235:genetics; D004032:Diet; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000235:genetics; D008268:Macular Degeneration / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008817:Mice, Mutant Strains; D011726:Pyridinium Compounds / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012176:Retinoids / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C112040:A2-E (N-retinylidene-N-retinylethanolamine); D000073883:CX3C Chemokine Receptor 1; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C471885:Cx3cr1 protein, mouse; D015525:Fatty Acids, Omega-3; D015850:Interleukin-6; D011726:Pyridinium Compounds; D019707:Receptors, Chemokine; D012176:Retinoids; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid