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Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of dry macular degeneration
  1. Ekatherine Prokopiou1,
  2. Panagiotis Kolovos1,
  3. Maria Kalogerou1,
  4. Anastasia Neokleous1,
  5. Gregory Papagregoriou2,
  6. Constantinos Deltas2,
  7. Stavros Malas3,
  8. Tassos Georgiou1
  1. 1Ophthalmos Research and Educational Institute, Nicosia, Cyprus
  2. 2Department of Biological Sciences, Molecular Medicine Research Centre and Laboratory of Molecular and Medical Genetics, University of Cyprus, Nicosia, Cyprus
  3. 3Developmental and Functional Genetics Group, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
  1. Correspondence to Dr Tassos Georgiou; tassosgeorgiou{at}hotmail.com

Abstract

Purpose To evaluate the therapeutic effects of omega-3 (ω-3) and omega-6 (ω-6) fatty acids in the CCL2−/− model of dry age-related macular degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1–1.5).

Methods Nine-month-old animals were allocated to different groups: (A) C57BL/6 untreated , (B) CCL2−/− untreated, (C) CCL2−/− treated with ω-3+ω-6, and (D) CCL2−/− treated with ω-3. Treatment was daily administered by gavage for 3 months. Fatty acids analysis was performed and retinas were histologically examined. Three-month-old wild type mice were used for comparison purposes. Real-time PCR and Western blot were performed for retinal inflammatory mediators.

Results Increased EPA and decreased AA levels were observed in both blood and retinas in the treatment groups. The outer nuclear layer thickness was increased in groups C (45.0±3.9 µm) and D (62.8±4.9 µm), compared with groups B (65.6±3.0 µm) and A (71.1±4.2 µm), and in younger mice, it was 98.0±3.9 µm. A decrease in NF-κB expression was noted in the treatment groups. Interleukin (IL) 18 protein levels demonstrated a significant reduction in the ω-3-treated group only.

Conclusion Supplementation with ω-3+ω-6 or ω-3 alone (AA/EPA=1–1.5) suggests a protective mechanism in the CCL2−/− animal model of dry AMD, with a more beneficial effect when ω-3 are used alone. Our findings indicated that inflammation is not the only determining factor; perhaps a regenerative process might be involved following administration of ω-3 fatty acids.

  • omega-3 fatty acids
  • inflammation
  • macular degeneration
  • retina
  • photoreceptors.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Acknowledgements The authors would like to thank Professor Heping Xu and Dr. Jose Manuel Romero (School of Medicine, Dentistry and Biochemical Sciences, Queen’s University Belfast, Ireland) for kindly providing training and support with regard to the experimental procedures. In addition, the authors would like to thank Mr Neoklis Makrides for his support throughout the study and Ms Andrea Christofides for her assistance in Western blotting.

  • Contributors EP planned and conducted the study, analysed the data and reported the results. PK, MK and AN were also involved in the experimental part of the study. GP helped with data analysis. CD and SM supported the study with guidance and provision of equipment. TG was responsible for the overall content of the study and provided guidance and support.

  • Competing interests TG has a patent for the treatment of eye diseases with omega-3 fatty acids.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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