Abstract
Omega-3 polyunsaturated fatty acids are essential nutrients for healthy individuals. Their beneficial effects in coronary and autoimmune diseases, as well as in diabetes, have been proven numerous times in the past. In addition, their role in maintaining normal physiology of the eyes has been extensively discussed over the last few years, with more emphasis given on their anti-inflammatory effects. From a literature review and some of our observational studies, there is strong evidence to support that supplementation of individuals with omega-3 formulations could lead to disease regression in some types of retinopathies, including age-related macular degeneration and macular dystrophies and also some severe forms of dry eyes. Therefore, using the right dosage regime and with the appropriate supervision, omega-3 supplementationĀ could be a potential therapeutic for different types of oculopathies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Sears B. The anti-inflammation zone. New York: HarperCollins; 2005.
Serhan CN, Arita M, Hong S, Gotlinger K. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids. 2004;39(11):1125ā32.
Bazan NG. Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Current Opin Clin Nutr Metab Care. 2007;10(2):136ā41.
Birch EE, Birch DG, Hoffman DR, Uauy R. Dietary essential fatty acid supply and visual acuity development. Invest Ophthalmol Vis Sci. 1992;33(11):3242ā53.
Friedman DS, OāColmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122(4):564ā72.
Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106ā16.
Miller JW. Age-related macular degeneration revisitedāpiecing the puzzle: the LXIX Edward Jackson memorial lecture. Am J Ophthalmol. 2013;155(1):1ā35, e13.
SanGiovanni JP, Agron E, Clemons TE, Chew EY. Omega-3 long-chain polyunsaturated fatty acid intake inversely associated with 12-year progression to advanced age-related macular degeneration. Arch Ophthalmol. 2009;127(1):110ā2.
Nag TC, Wadhwa S. Ultrastructure of the human retina in aging and various pathological states. Micron. 2012;43(7):759ā81.
Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298ā300.
Nussenblatt RB, Lee RW, Chew E, Wei L, Liu B, Sen HN, et al. Immune responses in age-related macular degeneration and a possible long-term therapeutic strategy for prevention. Am J Ophthalmol. 2014;158(1):5ā11, e2.
Macaulay R, Akbar AN, Henson SM. The role of the T cell in age-related inflammation. Age. 2013;35(3):563ā72.
Ferrara DC, Merriam JE, Freund KB, Spaide RF, Takahashi BS, Zhitomirsky I, et al. Analysis of major alleles associated with age-related macular degeneration in patients with multifocal choroiditis: strong association with complement factor H. Arch Ophthalmol. 2008;126(11):1562ā6.
Anderson DH, Radeke MJ, Gallo NB, Chapin EA, Johnson PT, Curletti CR, et al. The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retinal Eye Res. 2010;29(2):95ā112.
Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308(5720):385ā9.
Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005;308(5720):421ā4.
Gottfredsdottir MS, Sverrisson T, Musch DC, Stefansson E. Age related macular degeneration in monozygotic twins and their spouses in Iceland. Acta Ophthalmol Scand. 1999;77(4):422ā5.
Xu H, Chen M, Forrester JV. Para-inflammation in the aging retina. Prog Retinal Eye Res. 2009;28(5):348ā68.
Barouch FC, Miller JW. The role of inflammation and infection in age-related macular degeneration. Int Ophthalmol Clin. 2007;47(2):185ā97.
Penfold PL, Killingsworth MC, Sarks SH. Senile macular degeneration: the involvement of immunocompetent cells. Graefeās Arch Clin Exp Ophthalmol. 1985;223(2):69ā76 (Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie).
Penfold PL, Liew SC, Madigan MC, Provis JM. Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration. Invest Ophthalmol Vis Sci. 1997;38(10):2125ā33.
Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N. Association between C-reactive protein and age-related macular degeneration. JAMA. 2004;291(6):704ā10.
Seddon JM, George S, Rosner B, Rifai N. Progression of age-related macular degeneration: prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers. Arch Ophthalmol. 2005;123(6):774ā82.
Klein R, Klein BE, Marino EK, Kuller LH, Furberg C, Burke GL, et al. Early age-related maculopathy in the cardiovascular health study. Ophthalmology. 2003;110(1):25ā33.
Klein R, Klein BE, Knudtson MD, Wong TY, Shankar A, Tsai MY. Systemic markers of inflammation, endothelial dysfunction, and age-related maculopathy. Am J Ophthalmol. 2005;140(1):35ā44.
Libby P, Ridker PM. Inflammation and atherosclerosis: role of C-reactive protein in risk assessment. Am J Med. 2004;116(Suppl 6A):9Sā16S.
Cousins SW, Espinosa-Heidmann DG, Csaky KG. Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization? Arch Ophthalmol. 2004;122(7):1013ā8.
Gupta N, Brown KE, Milam AH. Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp Eye Res. 2003;76(4):463ā71.
Chen M, Forrester JV, Xu H. Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments. Exp Eye Res. 2007;84(4):635ā45.
Chen M, Muckersie E, Robertson M, Forrester JV, Xu H. Up-regulation of complement factor B in retinal pigment epithelial cells is accompanied by complement activation in the aged retina. Exp Eye Res. 2008;87(6):543ā50.
Coffey PJ, Gias C, McDermott CJ, Lundh P, Pickering MC, Sethi C, et al. Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction. Proc Natl Acad Sci USA. 2007;104(42):16651ā6.
Sohn JH, Kaplan HJ, Suk HJ, Bora PS, Bora NS. Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins. Invest Ophthalmol Vis Sci. 2000;41(11):3492ā502.
Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR. Group VISiONCT. Pegaptanib for neovascular age-related macular degeneration. New Engl J Med. 2004;351(27):2805ā16.
Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K. Group S-US. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120(11):2292ā9.
Age-Related Eye Disease Study Research G. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol. 2001;119(10):1439ā52.
SanGiovanni JP, Chew EY, Agron E, Clemons TE, Ferris FL 3rd, Gensler G, et al. The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23. Arch Ophthalmol. 2008;126(9):1274ā9.
Mishra A, Chaudhary A, Sethi S. Oxidized omega-3 fatty acids inhibit NF-kappaB activation via a PPARalpha-dependent pathway. Arterioscler Thromb Vasc Biol. 2004;24(9):1621ā7.
De Caterina R, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr. 2000;71(1 Suppl):213Sā23S.
Chen W, Esselman WJ, Jump DB, Busik JV. Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells. Invest Ophthalmol Vis Sci. 2005;46(11):4342ā7.
Rotstein NP, Politi LE, German OL, Girotti R. Protective effect of docosahexaenoic acid on oxidative stress-induced apoptosis of retina photoreceptors. Invest Ophthalmol Vis Sci. 2003;44(5):2252ā9.
Tuo J, Ross RJ, Herzlich AA, Shen D, Ding X, Zhou M, et al. A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration. Am J Pathol. 2009;175(2):799ā807.
Calder PC. Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients. Braz J Med Biol Res. 2003;36(4):433ā46 (Revista brasileira de pesquisas medicas e biologicas/ Sociedade Brasileira de Biofisica ).
Kapoor M, Kojima F, Yang L, Crofford LJ. Sequential induction of pro- and anti-inflammatory prostaglandins and peroxisome proliferators-activated receptor-gamma during normal wound healing: a time course study. Prostaglandins Leukot Essent Fatty Acids. 2007;76(2):103ā12.
Ramkumar HL, Tuo J, de Shen F, Zhang J, Cao X, Chew EY, et al. Nutrient supplementation with n3 polyunsaturated fatty acids, lutein, and zeaxanthin decrease A2E accumulation and VEGF expression in the retinas of Ccl2/Cx3cr1-deficient mice on Crb1rd8 background. J Nutr. 2013;143(7):1129ā35.
Tassos Georgiou AN, Nicolaou Despina, Sears Barry. Pilot study for treating dry age-related macular degeneration (AMD) with high-dose omega-3 fatty acids. PharmaNutr. 2014;2:8ā11.
Yanai R, Mulki L, Hasegawa E, Takeuchi K, Sweigard H, Suzuki J, et al. Cytochrome P450-generated metabolites derived from omega-3 fatty acids attenuate neovascularization. Proc Natl Acad Sci USA. 2014;111(26):9603ā8.
Webler AC, Michaelis UR, Popp R, Barbosa-Sicard E, Murugan A, Falck JR, et al. Epoxyeicosatrienoic acids are part of the VEGF-activated signaling cascade leading to angiogenesis. Am J Physiol Cell Physiol. 2008;295(5):C1292ā301.
Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY, Stephen Lee KS, et al. Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci USA. 2013;110(16):6530ā5.
Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, et al. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007;13(7):868ā73.
Rezende FA, Lapalme E, Qian CX, Smith LE, SanGiovanni JP, Sapieha P. Omega-3 supplementation combined with anti-vascular endothelial growth factor lowers vitreal levels of vascular endothelial growth factor in wet age-related macular degeneration. Am J Ophthalmol. 2014;158(5):1071ā8.
Dryja TP, McGee TL, Reichel E, Hahn LB, Cowley GS, Yandell DW, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 1990;343(6256):364ā6.
Kajiwara K, Hahn LB, Mukai S, Travis GH, Berson EL, Dryja TP. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa. Nature. 1991;354(6353):480ā3.
Cotran PR, Bruns GA, Berson EL, Dryja TP. Genetic analysis of patients with retinitis pigmentosa using a cloned cDNA probe for the human gamma subunit of cyclic GMP phosphodiesterase. Exp Eye Res. 1991;53(5):557ā64.
Wong P. Apoptosis, retinitis pigmentosa, and degeneration. Biochemistry Cell Biol. 1994;72(11ā12):489ā98 (Biochimie et biologie cellulaire).
Pruett RC. Retinitis pigmentosa: clinical observations and correlations. Trans Am Ophthalmol Soc. 1983;81:693ā735.
Newsome DA, Michels RG. Detection of lymphocytes in the vitreous gel of patients with retinitis pigmentosa. Am J Ophthalmol. 1988;105(6):596ā602.
Yoshida N, Ikeda Y, Notomi S, Ishikawa K, Murakami Y, Hisatomi T, et al. Clinical evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology. 2013;120(1):100ā5.
Bush RA, Malnoe A, Reme CE, Williams TP. Dietary deficiency of N-3 fatty acids alters rhodopsin content and function in the rat retina. Invest Ophthalmol Vis Sci. 1994;35(1):91ā100.
Yoshida N, Ikeda Y, Notomi S, Ishikawa K, Murakami Y, Hisatomi T, et al. Laboratory evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology. 2013;120(1):e5ā12.
Ebert S, Weigelt K, Walczak Y, Drobnik W, Mauerer R, Hume DA, et al. Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration. J Neurochem. 2009;110(6):1863ā75.
Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, et al. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol. 2004;122(9):1297ā305.
Hoffman DR, Locke KG, Wheaton DH, Fish GE, Spencer R, Birch DG. A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. Am J Ophthalmol. 2004;137(4):704ā18.
Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Willett WC. omega-3 intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2012;130(6):707ā11.
Hodge WG, Barnes D, Schachter HM, Pan YI, Lowcock EC, Zhang L, et al. The evidence for efficacy of omega-3 fatty acids in preventing or slowing the progression of retinitis pigmentosa: a systematic review. Can J Ophthalmol. 2006;41(4):481ā90 (Journal canadien dāophtalmologie).
Allikmets R. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997;17(1):122.
Delori FC, Staurenghi G, Arend O, Dorey CK, Goger DG, Weiter JJ. In vivo measurement of lipofuscin in Stargardtās diseaseāFundus flavimaculatus. Invest Ophthalmol Vis Sci. 1995;36(11):2327ā31.
Bernstein PS, Tammur J, Singh N, Hutchinson A, Dixon M, Pappas CM, et al. Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene. Invest Ophthalmol Vis Sci. 2001;42(13):3331ā6.
Molday RS, Zhang K. Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration. Prog Lipid Res. 2010;49(4):476ā92.
Guillou H, Zadravec D, Martin PG, Jacobsson A. The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. Prog Lipid Res. 2010;49(2):186ā99.
Barabas P, Liu A, Xing W, Chen CK, Tong Z, Watt CB, et al. Role of ELOVL4 and very long-chain polyunsaturated fatty acids in mouse models of Stargardt type 3 retinal degeneration. Proc Natl Acad Sci USA. 2013;110(13):5181ā6.
Agbaga MP, Brush RS, Mandal MN, Henry K, Elliott MH, Anderson RE. Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids. Proc Natl Acad Sci USA. 2008;105(35):12843ā8.
Dornstauder B, Suh M, Kuny S, Gaillard F, Macdonald IM, Clandinin MT, et al. Dietary docosahexaenoic acid supplementation prevents age-related functional losses and A2E accumulation in the retina. Invest Ophthalmol Vis Sci. 2012;53(4):2256ā65.
Querques G, Benlian P, Chanu B, Leveziel N, Coscas G, Soubrane G, et al. DHA supplementation for late onset Stargardt disease: NAT-3 study. Clin Ophthalmol. 2010;4:575ā80.
Sun H, Molday RS, Nathans J. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. J Biol Chem. 1999;274(12):8269ā81.
Maiti P, Kong J, Kim SR, Sparrow JR, Allikmets R, Rando RR. Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formation. Biochemistry. 2006;45(3):852ā60.
Gouze E, Pawliuk R, Pilapil C, Gouze JN, Fleet C, Palmer GD, et al. In vivo gene delivery to synovium by lentiviral vectors. Molecular Ther J Am Soc Gene Ther. 2002;5(4):397ā404.
Kostic C, Chiodini F, Salmon P, Wiznerowicz M, Deglon N, Hornfeld D, et al. Activity analysis of housekeeping promoters using self-inactivating lentiviral vector delivery into the mouse retina. Gene Ther. 2003;10(9):818ā21.
Jiang L, Baehr W. GCAP1 mutations associated with autosomal dominant cone dystrophy. Adv Exp Med Biol. 2010;664:273ā82.
Simunovic MP, Moore AT. The cone dystrophies. Eye. 1998;12(Pt 3b):553ā65.
Moore AT. Cone and cone-rod dystrophies. J Med Genet. 1992;29(5):289ā90.
Shiose S, Chen Y, Okano K, Roy S, Kohno H, Tang J, et al. Toll-like receptor 3 is required for development of retinopathy caused by impaired all-trans-retinal clearance in mice. J Biol Chem. 2011;286(17):15543ā55.
Lemp MA. Management of dry eye disease. Am J Manag Care. 2008;14(3 Suppl):S88ā101.
Pflugfelder SC. Prevalence, burden, and pharmacoeconomics of dry eye disease. Am J Manag Care. 2008;14(3 Suppl):S102ā6.
Uchino M, Schaumberg DA. Dry eye disease: impact on quality of life and vision. Current Ophthalmol Rep. 2013;1(2):51ā7.
Schiffman RM, Walt JG, Jacobsen G, Doyle JJ, Lebovics G, Sumner W. Utility assessment among patients with dry eye disease. Ophthalmology. 2003;110(7):1412ā9.
Schein OD, Munoz B, Tielsch JM, Bandeen-Roche K, West S. Prevalence of dry eye among the elderly. Am J Ophthalmol. 1997;124(6):723ā8.
The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop. The Ocular Surface. 2007;5(2):75ā92.
Tong L, Petznick A, Lee S, Tan J. Choice of artificial tear formulation for patients with dry eye: where do we start? Cornea. 2012;31(Suppl 1):S32ā6.
Alves M, Fonseca EC, Alves MF, Malki LT, Arruda GV, Reinach PS, et al. Dry eye disease treatment: a systematic review of published trials and a critical appraisal of therapeutic strategies. Ocul Surf. 2013;11(3):181ā92.
Asbell PA, Spiegel S. Ophthalmologist perceptions regarding treatment of moderate to severe dry eye: results of a physician survey. Trans Am Ophthalmol Soc. 2009;107:205ā10.
Kymionis GD, Bouzoukis DI, Diakonis VF, Siganos C. Treatment of chronic dry eye: focus on cyclosporine. Clin Ophthalmol. 2008;2(4):829ā36.
Enriquez-de-Salamanca A, Castellanos E, Stern ME, Fernandez I, Carreno E, Garcia-Vazquez C, et al. Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease. Mol Vis. 2010;16:862ā73.
McDermott AM, Perez V, Huang AJ, Pflugfelder SC, Stern ME, Baudouin C, et al. Pathways of corneal and ocular surface inflammation: a perspective from the cullen symposium. Ocul Surf. 2005;3(4 Suppl):S131ā8.
Pavesio CE, Decory HH. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol. 2008;92(4):455ā9.
Miljanovic B, Trivedi KA, Dana MR, Gilbard JP, Buring JE, Schaumberg DA. Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J Clin Nutr. 2005;82(4):887ā93.
Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:336ā56.
Brignole-Baudouin F, Baudouin C, Aragona P, Rolando M, Labetoulle M, Pisella PJ, et al. A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients. Acta Ophthalmol. 2011;89(7):e591ā7.
Rashid S, Jin Y, Ecoiffier T, Barabino S, Schaumberg DA, Dana MR. Topical omega-3 and omega-6 fatty acids for treatment of dry eye. Arch Ophthalmol. 2008;126(2):219ā25.
Kawakita T, Kawabata F, Tsuji T, Kawashima M, Shimmura S, Tsubota K. Effects of dietary supplementation with fish oil on dry eye syndrome subjects: randomized controlled trial. Biomed Res. 2013;34(5):215ā20.
Kangari H, Eftekhari MH, Sardari S, Hashemi H, Salamzadeh J, Ghassemi-Broumand M, et al. Short-term consumption of oral omega-3 and dry eye syndrome. Ophthalmology. 2013;120(11):2191ā6.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Georgiou, T., Prokopiou, E. (2016). Role of Omega-3 Fatty Acids for Eye Health. In: Hegde, M., Zanwar, A., Adekar, S. (eds) Omega-3 Fatty Acids. Springer, Cham. https://doi.org/10.1007/978-3-319-40458-5_20
Download citation
DOI: https://doi.org/10.1007/978-3-319-40458-5_20
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-40456-1
Online ISBN: 978-3-319-40458-5
eBook Packages: MedicineMedicine (R0)