An Eye to Health: Diet and Age-Related Macular Degeneration

Post on June 27, 2017 by André Broussard, D.C.

William C. Ou, BS; Charles C. Wykoff, MD, PhD

June 27, 2017

Age-related macular degeneration (AMD) is a leading cause of vision loss in the developed world, with advanced AMD affecting approximately 2 million people in the United States.[1,2] AMD is characterized by damage to the macula, the part of the retina responsible for central vision. In the advanced neovascular (or wet) form of AMD, abnormal blood vessels grow under and into the retina and can lead to severe loss of central vision due to secondary tissue disruption, exudation, and fibrosis.[1,3]

Although timely treatment with antiangiogenic agents given by intravitreal injection can minimize vision loss due to wet AMD, and indeed restore visual function in many cases,[4,5] currently there is no cure. Accordingly, there is a need to identify modifiable risk factors that can affect the development of AMD and its progression to advanced stages. For example, cigarette smoking[6] and obesity[7,8] have both been demonstrated to have a significant impact on AMD development and progression.

Does Diet Affect the Risk for AMD?

Substantial research, particularly within the past three decades, has been devoted to dietary and nutritional factors that may influence AMD development or progression.[9]

The retina appears to be highly susceptible to oxidative stress; such oxidative damage may play a role in AMD pathogenesis,[10] and therefore compounds that counteract oxidative damage may protect against both development and progression of AMD.[11,12,13,14]

The Age-Related Eye Disease Study (AREDS) found that a specific formulation of antioxidants and minerals, including vitamin C, vitamin E, beta-carotene, zinc, and copper, reduced the risk of patients with intermediate AMD developing the advanced form of the condition by 25% over 5 years.[12] Subsequently, the follow-up AREDS 2 study found that lutein and zeaxanthin can be substituted for beta-carotene, which has been linked to increased risk for lung cancer, particularly among former smokers.[13,15]

Beyond high-dose supplementation, intake of antioxidants and omega-3 long-chain polyunsaturated fatty acids through daily diet has also been reported to reduce AMD risk.[11,14,16]

Such findings have led many clinicians to recommend consumption of foods rich in these nutrients, including green, leafy vegetables (eg, spinach), fish, and whole grains (eg, brown rice).[1,11,14]

Similarly, epidemiologic studies have reported that a high glycemic index (GI) diet is a risk factor for AMD.[9,17] The GI represents a food’s impact on blood glucose levels relative to pure glucose (GI = 100). Consumption of higher-GI foods results in higher blood glucose levels. High GI foods (GI > 70) include white rice, white bread, and potatoes, whereas whole grains, lentils, and nonstarchy vegetables such as broccoli and cabbage have a low GI (GI < 55). High-GI diets are associated with accumulation of advanced glycation end-products (AGEs) that are formed when cellular proteins are modified by sugar molecules or their metabolites.[18] It has been suggested that AGEs may contribute to AMD pathogenesis at the molecular level by causing dysfunction of cellular protein editing and degradation in the outer retina and choroidal tissues.[9,18]

New Insights Into Dietary Impacts on AMD Development

Two studies published in 2012 reported that a low-GI diet can delay development of retinal lesions that precede AMD in mice.[18,19]

Building on these reports, a 2017 study by Rowan and colleagues[20] explored the ability of a low-GI diet to arrest high-GI diet-induced AMD-like features in mice, seeking to demonstrate a mechanistic link between diet and AMD by examining changes in metabolism and the gut microbiome.

In an effort to model diet-associated effects in mid-to-late adulthood in humans, middle-aged (12 months) mice were fed one of three diets until old age (24 months). The study diets included a low-GI diet (LG), a high-GI diet (HG), or a high-GI diet with a switch to a low-GI diet (HGxoLG) midway through the study.

HG mice developed many age-related features of AMD, including photoreceptor deterioration, retinal pigment epithelium atrophy, and accumulation of basal laminar deposits, whereas such changes appeared to be delayed in LG mice. Most strikingly, retinal damage was arrested or reversed in HGxoLG mice, ultimately making them nearly indistinguishable from LG mice when evaluated histologically. Higher levels of AGEs were found in HG mice than in LG mice, and analysis of plasma and urine metabolic profiles revealed that accumulation of lipids and lipid peroxidation end-products was associated with age-related features of AMD and an HG diet.

Furthermore, the authors demonstrated that the gut microbiome shifts in response to both aging and changes in diet, providing a mechanistic link between diet and metabolite profiles that influence AMD. A number of potential biomarkers for retinal damage were identified, including propionylcarnitine, lysophosphatidylethanolamine, and serotonin, the latter of which appears to be protective.

The authors concluded that changing from an HG to a LG diet, even during maturity, can protect against development of AMD. They also noted that changes in the gut microbiome and metabolome may facilitate these effects.

The strengths of this study include the well-designed experiments and a multifaceted approach to this complex problem. A clear and important limitation of the study, however, is the utilization of a mouse model. Animal models are a crucial part of biomedical research, and mouse models have been particularly instrumental in elucidating risk factors and processes that underlie AMD.[21] Nonetheless, it is an unfortunate reality that findings from animal studies can be difficult to translate into clinical practice, for reasons such as physiologic incompatibility.[22,23] Therefore, while the work of Rowan and colleagues offers much-needed insight into the mechanisms that link diet and AMD, these findings must be studied in humans before they can be used to inform management decisions and patient recommendations.

References:

  1. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008;358:2606-2617. Abstract
  2. Friedman DS, O’Colmain BJ, Muñoz B, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122:564-572. Abstract
  3. Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102:1640-1642. Abstract
  4. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431. Abstract
  5. Wykoff CC, Ou WC, Brown DM, et al. Randomized trial of treat-and-extend versus monthly dosing for neovascular age-related macular degeneration: 2-year results of the TREX-AMD Study. Ophthalmol Retina. 2 Feb 2017. [In press]
  6. Velilla S, García-Medina JJ, García-Layana A, et al. Smoking and age-related macular degeneration: review and update. J Ophthalmol. 2013;2013:895147.
  7. Seddon JM, Cote J, Davis N, Rosner B. Progression of age-related macular degeneration: association with body mass index, waist circumference, and waist-hip ratio. Arch Ophthalmol. 2003;121:785-792. Abstract
  8. Schaumberg DA, Christen WG, Hankinson SE, Glynn RJ. Body mass index and the incidence of visually significant age-related maculopathy in men. Arch Ophthalmol. 2001;119:1259-1265. Abstract
  9. Weikel KA, Chiu C-J, Taylor A. Nutritional modulation of age-related macular degeneration. Mol Aspects Med. 2012;33:318-375. Abstract
  10. Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000;45:115-134. Abstract
  11. Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. 1994;272:1413-1420. Abstract
  12. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417-1436. Abstract
  13. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309:2005-2015. Abstract
  14. van Leeuwen R, Boekhoorn S, Vingerling JR, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA. 2005;294:3101-3107. Abstract
  15. Aronow ME, Chew EY. Age-related Eye Disease Study 2: perspectives, recommendations, and unanswered questions. Curr Opin Ophthalmol. 2014;25:186-190. Abstract
  16. SanGiovanni JP, Chew EY, Clemons TE, et al. The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS Report No. 20. Arch Ophthalmol. 2007;125:671-679. Abstract
  17. Chiu C-J, Liu S, Willett WC, et al. Informing food choices and health outcomes by use of the dietary glycemic index. Nutr Rev. 2011;69:231-242. Abstract
  18. Uchiki T, Weikel KA, Jiao W, et al. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in nondiabetics). Aging Cell. 2012;11:1-13. Abstract
  19. Weikel KA, Fitzgerald P, Shang F, et al. Natural history of age-related retinal lesions that precede AMD in mice fed high or low glycemic index diets. Invest Ophthalmol Vis Sci. 2012;53:622-632. Abstract
  20. Rowan S, Jiang S, Korem T, et al. Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci. 2017;114:E4472-E4481. Abstract
  21. Pennesi ME, Neuringer M, Courtney RJ. Animal models of age related macular degeneration. Mol Aspects Med. 2012;33:487-509. Abstract
  22. van der Worp HB, Howells DW, Sena ES, et al. Can animal models of disease reliably inform human studies? PLoS Med. 2010;7:e1000245.
  23. Perrin S. Preclinical research: Make mouse studies work. Nature. 2014;507:423-425. Abstract

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