Macular degeneration risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Risk Factors

  • Smoking: The only environmental exposure clearly associated with macular degeneration is tobacco smoking. Exposure to cigarette smoke more than doubles the risk of macular degeneration.
  • Family history: The lifetime risk of developing late-stage macular degeneration is 50% for people who have a relative with macular degeneration v/s 12% for people who do not have relatives with macular degeneration, i.e. a fourfold higher risk.
  • Macular degeneration gene: The genes for the complement system proteins factor H (CFH) and factor B (CFB) have been determined to be strongly associated with a person's risk for developing macular degeneration. CFH is involved in inhibiting the inflammatory response mediated via C3b (and the alternative pathway of complement) both by acting as a co-factor for cleavage of C3b to its inactive form, C3bi, and by weakening the active complex that forms between C3b and factor B. C-reactive protein and polyanionic surface markers such as glycosaminoglycans normally enhance the ability of factor H to inhibit complement. But the mutation in CFH (Tyr402His) reduces the affinity of CFH for CRP and probably also alters the ability of factor H to recognize specific glycosaminoglycans. This change results in reduced ability of CFH to regulate complement on critical surfaces such as the specialized membrane at the back of the eye and leads to increased inflammatory response within the macula. In two 2006 studies at Yale Department of Epidemiology and Public Health and the Department of Ophthalmology and Visual Sciences, Moran Eye Center at the University of Utah School of Medicine, another gene that has implications for the disease, called HTRA1 (encoding a secreted serine protease), was identified.[1][2]
  • Arg80Gly Variant of the Complement Protein C3: A genetic study published in the New England Journal of Medicine in 2007 showed that a certain, common mutation in the C3 gene which is a central protein of the complement system is strongly associated with the occurrence of age-related macular degeneration.[3] This authors consider their study to underscore the influence of the complement pathway in the pathogenesis of this disease.
  • Hypertension: Also known as high blood pressure.
  • Cardiovascular status: High cholesterol, obesity.
  • High fat intake: It is associated with an increased risk of macular degeneration in both women and men. Fat provides about 42% of the food energy in the average American diet. A diet that derives closer to 20-25% of total food energy from fat is probably healthier. Reducing fat intake to this level means cutting down greatly on consumption of red meats and dairy products such as milk, cheese, and butter. Eating more cold-water fish[4] (at least twice weekly), rather than red meats, and eating any type of nuts may help macular degeneration patients.
  • Oxidative stress: It has been proposed that age related accumulation of low molecular weight, phototoxic, pro-oxidant melanin oligomers within lysosomes in the retinal pigment epithelium may be partly responsible for decreasing the digestive rate of photoreceptor outer rod segments (POS) by the RPE. A decrease in the digestive rate of POS has been shown to be associated with lipofuscin formation - a classic sign associated with macular degeneration.[5][6]
  • Exposure to sunlight: Especially blue light. There is conflicting evidence as to whether exposure to sunlight contributes to the development of macular degeneration. A recent study in the British Journal of Ophthalmology on 446 subjects found that it does not.[7] High energy visible light (HEV) has been implicated as a cause of age-related macular degeneration.[8][9]

References

  1. Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E, Li X, Chien J, Dewan A, Harmon J, Bernstein PS, Shridhar V, Zabriskie NA, Hoh J, Howes K, Zhang K. "A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration." Science. 2006 Nov 10;314(5801):992-3. PMID 17053109.
  2. Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, Tam PO, Chan WM, Lam DS, Snyder M, Barnstable C, Pang CP, Hoh J. "A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration". Science. 2006 Nov 10;314(5801):989-92. PMID 17053108
  3. Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT (2007). "Complement C3 Variant and the Risk of Age-Related Macular Degeneration". N Engl J Med. 357 (6): 553–561. PMID 17634448.
  4. John Paul SanGiovanni, ScD; Emily Y. Chew, MD; Traci E. Clemons, PhD; Matthew D. Davis, MD; Frederick L. Ferris III, MD; Gary R. Gensler, MS; Natalie Kurinij, PhD; Anne S. Lindblad, PhD; Roy C. Milton, PhD; Johanna M. Seddon, MD; and Robert D. Sperduto, MD (May 5, 2007). "The Relationship of Dietary Lipid Intake and Age-Related Macular Degeneration in a Case-Control Study". Archives of Ophthamology.
  5. "Melanin aggregation and polymerization: possible implications in age related macular degeneration." Ophthalmic Research, 2005; volume 37: pages 136-141.
  6. John Lacey, "Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration", 23-May-2006
  7. Khan, JC (2006). "Age related macular degeneration and sun exposure, iris colour, and skin sensitivity to sunlight". The British Journal of Ophthalmology. 90 (1): 29–32. PMID 16361662. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  8. Glazer-Hockstein, C (2006). "Could blue light-blocking lenses decrease the risk of age-related macular degeneration?". Retina. 26 (1): 1–4. PMID 16395131. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  9. Margrain, TH (2004). "Do blue light filters confer protection against age-related macular degeneration?". Progress in Retinal and Eye Research. 23 (5): 523–31. PMID 15302349. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)

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