Oxidative stress and systemic changes in age-related macular degeneration

Studies on Retinal and Choroidal Disorders

Volumn , Issue , 2012, Pages 367-397

  Brantley, Milam A ^a   Osborn, Melissa P ^a   Cai, Jiyang ^a   Sternberg, Paul ^a  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84883156227     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-61779-606-7_18     Document Type: Chapter

References (178)

1. Friedman DS, O'Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122(4):564-572. doi: 10.1001/archopht.122.4.564 122/4/564 [pii].
2. Jonasson F, Arnarsson A, Eiriksdottir G, Harris TB, Launer LJ, Meuer SM, Klein BE, Klein R, Gudnason V, Cotch MF (2011) Prevalence of age-related macular degeneration in old persons: age, gene/environment susceptibility Reykjavik study. Ophthalmology 118(5):825-30. doi: 10.1016/j.ophtha.2010.08.044.
3. Sarks J, Arnold J, Ho IV, Sarks S, Killingsworth M (2011) Evolution of reticular pseudodrusen. Br J Ophthalmol 95(7):979-85. doi: bjo.2010.194977 [pii] 10.1136/bjo.2010.194977.
4. Zweifel SA, Spaide RF, Curcio CA, Malek G, Imamura Y (2010) Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology 117(2):303-312 e201. doi: S0161-6420(09)00756-8 [pii] 10.1016/j.ophtha.2009.07.014.
5. Mullins RF, Russell SR, Anderson DH, Hageman GS (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14(7):835-846.
6. Wang L, Clark ME, Crossman DK, Kojima K, Messinger JD, Mobley JA, Curcio CA (2010) Abundant lipid and protein components of drusen. PLoS One 5(4):e10329. doi: 10.1371/journal. pone.0010329.
7. van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, de Jong PT (2003) The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study. Arch Ophthalmol 121(4):519-526. doi: 10.1001/archopht.121.4.519 121/4/519 [pii].
8. Age-Related Eye Disease Study Research Group (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 119(10):1417-36. doi: ecs10161 [pii].
9. Bressler NM, Bressler SB, Fine SL (1988) Age-related macular degeneration. Surv Ophthalmol 32(6):375-413.
10. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355(14):1419-1431. doi: 355/14/1419 [pii] 10.1056/NEJMoa054481.
11. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355(14):1432-1444. doi: 355/14/1432 [pii] 10.1056/NEJMoa062655.
12. Seddon JM, Cote J, Davis N, Rosner B (2003) Progression of age-related macular degeneration:association with body mass index, waist circumference, and waist-hip ratio. Arch Ophthalmol 121(6):785-792. doi: 10.1001/archopht.121.6.785 121/6/785 [pii].
13. Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd (2005) Risk factors for the incidence of advanced age-related macular degeneration in the age-related eye disease study (AREDS) AREDS report no. 19. Ophthalmology 112(4):533-539. doi: S0161-6420(04)01794-4[pii] 10.1016/j.ophtha.2004.10.047.
14. Tan JS, Mitchell P, Kifley A, Flood V, Smith W, Wang JJ (2007) Smoking and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Arch Ophthalmol 125(8):1089-1095. doi: 125/8/1089 [pii] 10.1001/archopht.125.8.1089.
15. Cackett P, Wong TY, Aung T, Saw SM, Tay WT, Rochtchina E, Mitchell P, Wang JJ (2008) Smoking, cardiovascular risk factors, and age-related macular degeneration in Asians: the Singapore Malay Eye Study. Am J Ophthalmol 146(6):960-967 e961. doi: S0002-9394(08)00514-X [pii] 10.1016/j.ajo.2008.06.026.
16. Chakravarthy U, Augood C, Bentham GC, de Jong PT, Rahu M, Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Vioque J, Young IS, Fletcher AE (2007) Cigarette smoking and age-related macular degeneration in the EUREYE Study. Ophthalmology 114(6):1157-1163. doi: S0161-6420(06)01324-8 [pii] 10.1016/j.ophtha.2006.09.022.
17. Fraser-Bell S, Wu J, Klein R, Azen SP, Varma R (2006) Smoking, alcohol intake, estrogen use, and age-related macular degeneration in Latinos: the Los Angeles Latino Eye Study. Am J Ophthalmol 141(1):79-87. doi: S0002-9394(05)00907-4 [pii] 10.1016/j.ajo.2005.08.024.
18. Klein R, Knudtson MD, Cruickshanks KJ, Klein BE (2008) Further observations on the association between smoking and the long-term incidence and progression of age-related macular degeneration: the Beaver Dam Eye Study. Arch Ophthalmol 126(1):115-121. doi: 126/1/115[pii] 10.1001/archopht.126.1.115.
19. Tomany SC, Wang JJ, Van Leeuwen R, Klein R, Mitchell P, Vingerling JR, Klein BE, Smith W, De Jong PT (2004) Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology 111(7):1280-1287. doi: 10.1016/j.ophtha.2003.11.010 S0161-6420(04)00306-9 [pii].
20. Khan JC, Thurlby DA, Shahid H, Clayton DG, Yates JR, Bradley M, Moore AT, Bird AC (2006) Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation. Br J Ophthalmol 90(1):75-80. doi: 90/1/75 [pii] 10.1136/bjo.2005.073643.
21. Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT et al (1994) Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 272(18):1413-1420.
22. van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, de Jong PT (2005) Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 294(24):3101-3107. doi: 294/24/3101 [pii] 10.1001/jama.294.24.3101.
23. Hammond CJ, Webster AR, Snieder H, Bird AC, Gilbert CE, Spector TD (2002) Genetic influence on early age-related maculopathy: a twin study. Ophthalmology 109(4):730-736. doi: S0161-6420(01)01049-1 [pii].
24. Seddon JM, Cote J, Page WF, Aggen SH, Neale MC (2005) The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences. Arch Ophthalmol 123(3):321-327. doi: 123/3/321 [pii] 10.1001/archopht.123.3.321.
25. Haddad S, Chen CA, Santangelo SL, Seddon JM (2006) The genetics of age-related macular degeneration: a review of progress to date. Surv Ophthalmol 51(4):316-363. doi: S0039-6257(06)00091-9 [pii] 10.1016/j.survophthal.2006.05.001.
26. Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308(5720):421-424. doi: 1110189 [pii] 10.1126/science.1110189.
27. Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308(5720):419-421. doi: 1110359 [pii] 10.1126/science.1110359.
28. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308(5720):385-389. doi: 1109557 [pii] 10.1126/science.1109557.
29. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 102(20):7227-7232. doi: 0501536102 [pii]10.1073/pnas.0501536102.
30. Zareparsi S, Branham KE, Li M, Shah S, Klein RJ, Ott J, Hoh J, Abecasis GR, Swaroop A (2005) Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration. Am J Hum Genet 77(1):149-153. doi: S0002-9297(07)60911-2 [pii] 10.1086/431426.
31. Souied EH, Leveziel N, Richard F, Dragon-Durey MA, Coscas G, Soubrane G, Benlian P, Fremeaux-Bacchi V (2005) Y402H complement factor H polymorphism associated with exudative age-related macular degeneration in the French population. Mol Vis 11:1135-1140. doi: v11/a131 [pii].
32. Simonelli F, Frisso G, Testa F, di Fiore R, Vitale DF, Manitto MP, Brancato R, Rinaldi E, Sacchetti L (2006) Polymorphism p. 402Y>H in the complement factor H protein is a risk factor for age related macular degeneration in an Italian population. Br J Ophthalmol 90(9):1142-1145. doi: bjo.2006.096487 [pii] 10.1136/bjo.2006.096487.
33. Despriet DD, Klaver CC, Witteman JC, Bergen AA, Kardys I, de Maat MP, Boekhoorn SS, Vingerling JR, Hofman A, Oostra BA, Uitterlinden AG, Stijnen T, van Duijn CM, de Jong PT (2006) Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. JAMA 296(3):301-309. doi: 296/3/301 [pii] 10.1001/jama.296.3.301.
34. Seitsonen S, Lemmela S, Holopainen J, Tommila P, Ranta P, Kotamies A, Moilanen J, Palosaari T, Kaarniranta K, Meri S, Immonen I, Jarvela I (2006) Analysis of variants in the complement factor H, the elongation of very long chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular degeneration in the Finnish population. Mol Vis 12:796-801. doi: v12/a89 [pii].
35. Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Hageman GS, Dean M, Allikmets R (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet 38(4):458-462. doi: ng1750 [pii] 10.1038/ng1750.
36. 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. doi: NEJMoa072618 [pii] 10.1056/NEJMoa072618.
37. Fagerness JA, Maller JB, Neale BM, Reynolds RC, Daly MJ, Seddon JM (2009) Variation near complement factor I is associated with risk of advanced AMD. Eur J Hum Genet 17(1):100-104. doi: ejhg2008140 [pii] 10.1038/ejhg.2008.140.
38. Ennis S, Gibson J, Cree AJ, Collins A, Lotery AJ (2010) Support for the involvement of complement factor I in age-related macular degeneration. Eur J Hum Genet 18(1):15-16. doi: ejhg2009113 [pii] 10.1038/ejhg.2009.113.
39. Hageman GS, Hancox LS, Taiber AJ, Gehrs KM, Anderson DH, Johnson LV, Radeke MJ, Kavanagh D, Richards A, Atkinson J, Meri S, Bergeron J, Zernant J, Merriam J, Gold B, Allikmets R, Dean M (2006) Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann Med 38(8):592-604.
40. Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U (2006) A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat Genet 38(10):1173-1177. doi: ng1890 [pii] 10.1038/ng1890.
41. Ennis S, Jomary C, Mullins R, Cree A, Chen X, Macleod A, Jones S, Collins A, Stone E, Lotery A (2008) Association between the SERPING1 gene and age-related macular degeneration:a two-stage case-control study. Lancet 372(9652):1828-1834. doi: S0140-6736(08)61348-3 [pii] 10.1016/S0140-6736(08)61348-3.
42. Lee AY, Kulkarni M, Fang AM, Edelstein S, Osborn MP, Brantley MA (2010) The effect of genetic variants in SERPING1 on the risk of neovascular age-related macular degeneration. Br J Ophthalmol 94(7):915-917. doi: 94/7/915 [pii] 10.1136/bjo.2009.172007.
43. Jakobsdottir J, Conley YP, Weeks DE, Mah TS, Ferrell RE, Gorin MB (2005) Susceptibility genes for age-related maculopathy on chromosome 10q26. Am J Hum Genet 77(3):389-407. doi: S0002-9297(07)63020-1 [pii] 10.1086/444437.
44. Rivera A, Fisher SA, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, Weber BH (2005) Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet 14(21):3227-3236. doi: ddi353 [pii] 10.1093/hmg/ddi353.
45. 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 (2006) A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science 314(5801):992-993. doi: 1133811 [pii] 10.1126/science.1133811.
46. 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 (2006) HTRA1 promoter polymorphism in wet agerelated macular degeneration. Science 314(5801):989-992. doi: 1133807 [pii] 10.1126/ science.1133807.
47. Kanda A, Chen W, Othman M, Branham KE, Brooks M, Khanna R, He S, Lyons R, Abecasis GR, Swaroop A (2007) A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci USA 104(41):16227-16232. doi: 0703933104 [pii] 10.1073/pnas.0703933104.
48. Wang G, Spencer KL, Court BL, Olson LM, Scott WK, Haines JL, Pericak-Vance MA (2009) Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria. Invest Ophthalmol Vis Sci 50(7):3084-3090. doi: iovs.08-3240 [pii] 10.1167/ iovs.08-3240.
49. Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, Raychaudhuri S, Tan PL, Oh EC, Merriam JE, Souied E, Bernstein PS, Li B, Frederick JM, Zhang K, Brantley MA Jr, Lee AY, Zack DJ, Campochiaro B, Campochiaro P, Ripke S, Smith RT, Barile GR, Katsanis N, Allikmets R, Daly MJ, Seddon JM (2010) Genome-wide association study of advanced agerelated macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci USA 107(16):7395-7400. doi: 0912019107 [pii] 10.1073/pnas.0912019107.
50. Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, Tosakulwong N, Pericak-Vance MA, Campochiaro PA, Klein ML, Tan PL, Conley YP, Kanda A, Kopplin L, Li Y, Augustaitis KJ, Karoukis AJ, Scott WK, Agarwal A, Kovach JL, Schwartz SG, Postel EA, Brooks M, Baratz KH, Brown WL, Brucker AJ, Orlin A, Brown G, Ho A, Regillo C, Donoso L, Tian L, Kaderli B, Hadley D, Hagstrom SA, Peachey NS, Klein R, Klein BE, Gotoh N, Yamashiro K, Ferris Iii F, Fagerness JA, Reynolds R, Farrer LA, Kim IK, Miller JW, Corton M, Carracedo A, Sanchez-Salorio M, Pugh EW, Doheny KF, Brion M, Deangelis MM, Weeks DE, Zack DJ, Chew EY, Heckenlively JR, Yoshimura N, Iyengar SK, Francis PJ, Katsanis N, Seddon JM, Haines JL, Gorin MB, Abecasis GR, Swaroop A (2010) Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci USA 107(16):7401-7406. doi: 0912702107 [pii] 10.1073/pnas.0912702107.
51. Seddon JM, Reynolds R, Rosner B (2010) Associations of smoking, body mass index, dietary lutein, and the LIPC gene variant rs10468017 with advanced age-related macular degeneration. Mol Vis 16:2412-2424.
52. Weber BH, Vogt G, Pruett RC, Stohr H, Felbor U (1994) Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat Genet 8(4):352-356. doi: 10.1038/ng1294-352.
53. Li Z, Clarke MP, Barker MD, McKie N (2005) TIMP3 mutation in Sorsby's fundus dystrophy:molecular insights. Expert Rev Mol Med 7(24):1-15. doi: S1462399405010045 [pii] 10.1017/S1462399405010045.
54. Khandhadia S, Lotery A (2010) Oxidation and age-related macular degeneration: insights from molecular biology. Expert Rev Mol Med 12:e34. doi: S146239941000164X [pii] 10.1017/S146239941000164X.
55. Winkler BS, Boulton ME, Gottsch JD, Sternberg P (1999) Oxidative damage and age-related macular degeneration. Mol Vis 5:32.
56. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107(9):1058-1070. doi: 107/9/1058 [pii] 10.1161/CIRCRESAHA.110.223545.
57. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP (2000) Oxidative damage and protection of the RPE. Prog Retin Eye Res 19(2):205-221.
58. Beatty S, Koh H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45(2):115-134. doi: S0039625700001405 [pii].
59. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59(3):527-605.
60. Borish ET, Pryor WA, Venugopal S, Deutsch WA (1987) DNA synthesis is blocked by cigarette tar-induced DNA single-strand breaks. Carcinogenesis 8(10):1517-1520.
61. Jones DP, Mody VC Jr, Carlson JL, Lynn MJ, Sternberg P Jr (2002) Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses. Free Radic Biol Med 33(9):1290-1300. doi: S0891584902010407 [pii].
62. Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan L, Rayborn ME, Salomon RG, Hollyfield JG (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci USA 99(23):14682-14687. doi: 10.1073/pnas.222551899 222551899 [pii].
63. Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE (2001) Macular pigment in donor eyes with and without AMD: a case-control study. Invest Ophthalmol Vis Sci 42(1):235-240.
64. Bernstein PS, Zhao DY, Wintch SW, Ermakov IV, McClane RW, Gellermann W (2002) Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients. Ophthalmology 109(10):1780-1787. doi: S0161-6420(02)01173-9 [pii].
65. Obana A, Hiramitsu T, Gohto Y, Ohira A, Mizuno S, Hirano T, Bernstein PS, Fujii H, Iseki K, Tanito M, Hotta Y (2008) Macular carotenoid levels of normal subjects and age-related maculopathy patients in a Japanese population. Ophthalmology 115(1):147-157. doi: S0161-6420(07)00218-7 [pii] 10.1016/j.ophtha.2007.02.028.
66. SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD (2007) The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol 125(9):1225-1232. doi: 125/9/1225 [pii] 10.1001/archopht.125.9.1225.
67. Scholl HP, Charbel Issa P, Walier M, Janzer S, Pollok-Kopp B, Borncke F, Fritsche LG, Chong NV, Fimmers R, Wienker T, Holz FG, Weber BH, Oppermann M (2008) Systemic complement activation in age-related macular degeneration. PLoS One 3(7):e2593. doi: 10.1371/journal.pone.0002593.
68. Reynolds R, Hartnett ME, Atkinson JP, Giclas PC, Rosner B, Seddon JM (2009) Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes. Invest Ophthalmol Vis Sci 50(12):5818-5827. doi: iovs.09-3928 [pii] 10.1167/iovs.09-3928.
69. Huang SJ, Costa DL, Gross NE, Yannuzzi LA (2003) Peripheral drusen in membranoproliferative glomerulonephritis type II. Retina 23(3):429-431.
70. Jones DP, Carlson JL, Samiec PS, Sternberg P Jr, Mody VC Jr, Reed RL, Brown LA (1998) Glutathione measurement in human plasma. Evaluation of sample collection, storage and derivatization conditions for analysis of dansyl derivatives by HPLC. Clin Chim Acta 275(2):175-184. doi: S0009-8981(98)00089-8 [pii].
71. Samiec PS, Drews-Botsch C, Flagg EW, Kurtz JC, Sternberg P Jr, Reed RL, Jones DP (1998) Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Free Radic Biol Med 24(5):699-704. doi: S0891-5849(97)00286-4 [pii].
72. Jarrett SG, Lewin AS, Boulton ME (2010) The importance of mitochondria in agerelated and inherited eye disorders. Ophthalmic Res 44(3):179-190. doi: 000316480 [pii] 10.1159/000316480.
73. Feher J, Kovacs I, Artico M, Cavallotti C, Papale A, Balacco Gabrieli C (2006) Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Aging 27(7):983-993. doi: S0197-4580(05)00154-5 [pii] 10.1016/j.neurobiolaging.2005.05.012.
74. Nordgaard CL, Berg KM, Kapphahn RJ, Reilly C, Feng X, Olsen TW, Ferrington DA (2006) Proteomics of the retinal pigment epithelium reveals altered protein expression at progressive stages of age-related macular degeneration. Invest Ophthalmol Vis Sci 47(3):815-822. doi: 47/3/815 [pii] 10.1167/iovs.05-0976.
75. Nordgaard CL, Karunadharma PP, Feng X, Olsen TW, Ferrington DA (2008) Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration. Invest Ophthalmol Vis Sci 49(7):2848-2855. doi: iovs.07-1352 [pii] 10.1167/ iovs.07-1352.
76. Karunadharma PP, Nordgaard CL, Olsen TW, Ferrington DA (2010) Mitochondrial DNA damage as a potential mechanism for age-related macular degeneration. Invest Ophthalmol Vis Sci 51(11):5470-5479. doi: iovs.10-5429 [pii] 10.1167/iovs.10-5429.
77. Gorgun E, Guven M, Unal M, Batar B, Guven GS, Yenerel M, Tatlipinar S, Seven M, Yuksel A (2010) Polymorphisms of the DNA repair genes XPD and XRCC1 and the risk of agerelated macular degeneration. Invest Ophthalmol Vis Sci 51(9):4732-4737. doi: iovs.09-4842 [pii] 10.1167/iovs.09-4842.
78. Totan Y, Yagci R, Bardak Y, Ozyurt H, Kendir F, Yilmaz G, Sahin S, Sahin Tig U (2009) Oxidative macromolecular damage in age-related macular degeneration. Curr Eye Res 34(12):1089-1093. doi: 10.3109/02713680903353772.
79. Lau LI, Liu CJ, Wei YH (2010) Increase of 8-hydroxy-2 ¢ -deoxyguanosine in aqueous humor of patients with exudative age-related macular degeneration. Invest Ophthalmol Vis Sci 51(11):5486-5490. doi: iovs.10-5663 [pii] 10.1167/iovs.10-5663.
80. Szaflik JP, Janik-Papis K, Synowiec E, Ksiazek D, Zaras M, Wozniak K, Szaflik J, Blasiak J (2009) DNA damage and repair in age-related macular degeneration. Mutat Res 669(1-2):169-176. doi: S0027-5107(09)00210-3 [pii] 10.1016/j.mrfmmm.2009.06.008.
81. Coral K, Raman R, Rathi S, Rajesh M, Sulochana KN, Angayarkanni N, Paul PG, Ramakrishnan S (2006) Plasma homocysteine and total thiol content in patients with exudative age-related macular degeneration. Eye (Lond) 20(2):203-207. doi: 6701853 [pii] 10.1038/ sj.eye.6701853.
82. Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G et al (1997) Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 277(22):1775-1781.
83. Rochtchina E, Wang JJ, Flood VM, Mitchell P (2007) Elevated serum homocysteine, low serum vitamin B12, folate, and age-related macular degeneration: the Blue Mountains Eye Study. Am J Ophthalmol 143(2):344-346. doi: S0002-9394(06)01016-6 [pii] 10.1016/j. ajo.2006.08.032.
84. Seddon JM, Gensler G, Klein ML, Milton RC (2006) Evaluation of plasma homocysteine and risk of age-related macular degeneration. Am J Ophthalmol 141(1):201-203. doi: S0002-9394(05)00861-5 [pii] 10.1016/j.ajo.2005.07.059.
85. Ates O, Azizi S, Alp HH, Kiziltunc A, Beydemir S, Cinici E, Kocer I, Baykal O (2009) Decreased serum paraoxonase 1 activity and increased serum homocysteine and malondialdehyde levels in age-related macular degeneration. Tohoku J Exp Med 217(1):17-22. doi: JST. JSTAGE/tjem/217.17 [pii].
86. Nowak M, Swietochowska E, Wielkoszynski T, Marek B, Karpe J, Gorski J, Glogowska-Szelag J, Kos-Kudla B, Ostrowska Z (2003) Changes in blood antioxidants and several lipid peroxidation products in women with age-related macular degeneration. Eur J Ophthalmol 13(3):281-286.
87. Vine AK, Stader J, Branham K, Musch DC, Swaroop A (2005) Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. Ophthalmology 112(12):2076-2080. doi: S0161-6420(05)00895-X [pii] 10.1016/j.ophtha.2005.07.004.
88. Kamburoglu G, Gumus K, Kadayifcilar S, Eldem B (2006) Plasma homocysteine, vitamin B12 and folate levels in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 244(5):565-569. doi: 10.1007/s00417-005-0108-2.
89. Axer-Siegel R, Bourla D, Ehrlich R, Dotan G, Benjamini Y, Gavendo S, Weinberger D, Sela BA (2004) Association of neovascular age-related macular degeneration and hyperhomocysteinemia. Am J Ophthalmol 137(1):84-89. doi: S000293940300864X [pii].
90. Wu KH, Tan AG, Rochtchina E, Favaloro EJ, Williams A, Mitchell P, Wang JJ (2007) Circulating inflammatory markers and hemostatic factors in age-related maculopathy: a population- based case-control study. Invest Ophthalmol Vis Sci 48(5):1983-1988. doi: 48/5/1983 [pii] 10.1167/iovs.06-0223.
91. Heuberger RA, Fisher AI, Jacques PF, Klein R, Klein BE, Palta M, Mares-Perlman JA (2002) Relation of blood homocysteine and its nutritional determinants to age-related maculopathy in the third National Health and Nutrition Examination Survey. Am J Clin Nutr 76(4):897-902.
92. Fliesler SJ, Anderson RE (1983) Chemistry and metabolism of lipids in the vertebrate retina. Prog Lipid Res 22(2):79-131.
93. Gu X, Meer SG, Miyagi M, Rayborn ME, Hollyfield JG, Crabb JW, Salomon RG (2003) Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age-related macular degeneration. J Biol Chem 278(43):42027-42035. doi: 10.1074/jbc.M305460200 M305460200 [pii].
94. Gu J, Pauer GJ, Yue X, Narendra U, Sturgill GM, Bena J, Gu X, Peachey NS, Salomon RG, Hagstrom SA, Crabb JW (2009) Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers. Mol Cell Proteomics 8(6):1338-1349. doi: M800453-MCP200 [pii] 10.1074/mcp.M800453-MCP200.
95. Ebrahem Q, Renganathan K, Sears J, Vasanji A, Gu X, Lu L, Salomon RG, Crabb JW, Anand-Apte B (2006) Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization:implications for age-related macular degeneration. Proc Natl Acad Sci USA 103(36):13480-13484. doi: 0601552103 [pii] 10.1073/pnas.0601552103.
96. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11(1):81-128.
97. Schutt F, Bergmann M, Holz FG, Kopitz J (2003) Proteins modified by malondialdehyde, 4-hydroxynonenal, or advanced glycation end products in lipofuscin of human retinal pigment epithelium. Invest Ophthalmol Vis Sci 44(8):3663-3668.
98. Krohne TU, Holz FG, Kopitz J (2010) Apical-to-basolateral transcytosis of photoreceptor outer segments induced by lipid peroxidation products in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 51(1):553-560. doi: iovs.09-3755 [pii] 10.1167/iovs.09-3755.
99. Ethen CM, Reilly C, Feng X, Olsen TW, Ferrington DA (2007) Age-related macular degeneration and retinal protein modification by 4-hydroxy-2-nonenal. Invest Ophthalmol Vis Sci 48(8):3469-3479. doi: 48/8/3469 [pii] 10.1167/iovs.06-1058.
100. Totan Y, Cekic O, Borazan M, Uz E, Sogut S, Akyol O (2001) Plasma malondialdehyde and nitric oxide levels in age related macular degeneration. Br J Ophthalmol 85(12):1426-1428.
101. Yildirim O, Ates NA, Tamer L, Muslu N, Ercan B, Atik U, Kanik A (2004) Changes in antioxidant enzyme activity and malondialdehyde level in patients with age-related macular degeneration. Ophthalmologica 218(3):202-206. doi: 10.1159/000076845 OPH2004218003202 [pii].
102. Evereklioglu C, Er H, Doganay S, Cekmen M, Turkoz Y, Otlu B, Ozerol E (2003) Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration. Doc Ophthalmol 106(2):129-136.
103. Ashraf MZ, Kar NS, Podrez EA (2009) Oxidized phospholipids: biomarker for cardiovascular diseases. Int J Biochem Cell Biol 41(6):1241-1244. doi: S1357-2725(08)00472-X [pii] 10.1016/j.biocel.2008.11.002.
104. Suzuki M, Kamei M, Itabe H, Yoneda K, Bando H, Kume N, Tano Y (2007) Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration. Mol Vis 13:772-778. doi: v13/a84 [pii].
105. Ikeda T, Obayashi H, Hasegawa G, Nakamura N, Yoshikawa T, Imamura Y, Koizumi K, Kinoshita S (2001) Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration. Am J Ophthalmol 132(2):191-195. doi: S0002939401009758 [pii].
106. Javadzadeh A, Ghorbanihaghjo A, Rashtchizadeh N, Rafeey M, Rahimi-Ardabili B (2007) Enhanced susceptibility of low-density lipoprotein to oxidation in wet type age-related macular degeneration in male patients. Saudi Med J 28(2):221-224. doi: 20060689' [pii].
107. Frei B, England L, Ames BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 86(16):6377-6381.
108. Yin J, Thomas F, Lang JC, Chaum E (2011) Modulation of oxidative stress responses in the human retinal pigment epithelium following treatment with vitamin C. J Cell Physiol 226(8):2025-32. doi: 10.1002/jcp. 22532.
109. Simonelli F, Zarrilli F, Mazzeo S, Verde V, Romano N, Savoia M, Testa F, Vitale DF, Rinaldi M, Sacchetti L (2002) Serum oxidative and antioxidant parameters in a group of Italian patients with age-related maculopathy. Clin Chim Acta 320(1-2):111-115. doi: S0009898102000566 [pii].
110. Michikawa T, Ishida S, Nishiwaki Y, Kikuchi Y, Tsuboi T, Hosoda K, Ishigami A, Iwasawa S, Nakano M, Takebayashi T (2009) Serum antioxidants and age-related macular degeneration among older Japanese. Asia Pac J Clin Nutr 18(1):1-7.
111. Eye Disease Case-Control Study Group (1993) Antioxidant status and neovascular agerelated macular degeneration. Arch Ophthalmol 111(1):104-109.
112. Blumenkranz MS, Russell SR, Robey MG, Kott-Blumenkranz R, Penneys N (1986) Risk factors in age-related maculopathy complicated by choroidal neovascularization. Ophthalmology 93(5):552-558.
113. Hogg R, Chakravarthy U (2004) AMD and micronutrient antioxidants. Curr Eye Res 29(6):387-401. doi: YXKW9T01GF7JYXJU [pii] 10.1080/02713680490517890.
114. Delcourt C, Cristol JP, Tessier F, Leger CL, Descomps B, Papoz L (1999) Age-related macular degeneration and antioxidant status in the POLA study. POLA Study Group. Pathologies Oculaires Liees a l'Age. Arch Ophthalmol 117(10):1384-1390.
115. Yilmaz T, Aydemir O, Ozercan IH, Ustundag B (2007) Effects of vitamin e, pentoxifylline and aprotinin on light-induced retinal injury. Ophthalmologica 221(3):159-166. doi: 000099295 [pii] 10.1159/000099295.
116. Belda JI, Roma J, Vilela C, Puertas FJ, Diaz-Llopis M, Bosch-Morell F, Romero FJ (1999) Serum vitamin E levels negatively correlate with severity of age-related macular degeneration. Mech Ageing Dev 107(2):159-164. doi: S0047637498001444 [pii].
117. Mares-Perlman JA, Brady WE, Klein R, Klein BE, Bowen P, Stacewicz-Sapuntzakis M, Palta M (1995) Serum antioxidants and age-related macular degeneration in a population-based case-control study. Arch Ophthalmol 113(12):1518-1523.
118. Young AJ, Lowe GM (2001) Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys 385(1):20-27. doi: S0003-9861(00)92149-0 [pii] 10.1006/abbi.2000.2149.
119. Chucair AJ, Rotstein NP, Sangiovanni JP, During A, Chew EY, Politi LE (2007) Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: relation with docosahexaenoic acid. Invest Ophthalmol Vis Sci 48(11):5168-5177. doi: 48/11/5168 [pii] 10.1167/iovs.07-0037.
120. Nakajima Y, Shimazawa M, Otsubo K, Ishibashi T, Hara H (2009) Zeaxanthin, a retinal carotenoid, protects retinal cells against oxidative stress. Curr Eye Res 34(4):311-318. doi: 910502194 [pii] 10.1080/02713680902745408.
121. Berendschot TT, Willemse-Assink JJ, Bastiaanse M, de Jong PT, van Norren D (2002) Macular pigment and melanin in age-related maculopathy in a general population. Invest Ophthalmol Vis Sci 43(6):1928-1932.
122. Ciulla TA, Hammond BR Jr (2004) Macular pigment density and aging, assessed in the normal elderly and those with cataracts and age-related macular degeneration. Am J Ophthalmol 138(4):582-587. doi: S0002-9394(04)00604-X [pii] 10.1016/j.ajo.2004.05.057.
123. Kanis MJ, Berendschot TT, van Norren D (2007) Influence of macular pigment and melanin on incident early AMD in a white population. Graefes Arch Clin Exp Ophthalmol 245(6):767-773. doi: 10.1007/s00417-006-0478-0.
124. Robman L, Vu H, Hodge A, Tikellis G, Dimitrov P, McCarty C, Guymer R (2007) Dietary lutein, zeaxanthin, and fats and the progression of age-related macular degeneration. Can J Ophthalmol 42(5):720-726. doi: i07-116 [pii] 10.1139/i07-116.
125. Beatty S, van Kuijk FJ, Chakravarthy U (2008) Macular pigment and age-related macular degeneration: longitudinal data and better techniques of measurement are needed. Invest Ophthalmol Vis Sci 49(3):843-845. doi: 49/3/843 [pii] 10.1167/iovs.07-1276.
126. Hogg RE, Anderson RS, Stevenson MR, Zlatkova MB, Chakravarthy U (2007) In vivo macular pigment measurements: a comparison of resonance Raman spectroscopy and heterochromatic flicker photometry. Br J Ophthalmol 91(4):485-490. doi: bjo.2006.090936 [pii] 10.1136/bjo.2006.090936.
127. Cardinault N, Abalain JH, Sairafi B, Coudray C, Grolier P, Rambeau M, Carre JL, Mazur A, Rock E (2005) Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age-related macular degeneration patients. Clin Chim Acta 357(1):34-42. doi: S0009-8981(05)00105-1 [pii] 10.1016/j.cccn.2005.01.030.
128. Liang FQ, Green L, Wang C, Alssadi R, Godley BF (2004) Melatonin protects human retinal pigment epithelial (RPE) cells against oxidative stress. Exp Eye Res 78(6):1069-1075. doi: 10.1016/j.exer.2004.02.003 S0014483504000582 [pii].
129. Rosen R, Hu DN, Perez V, Tai K, Yu GP, Chen M, Tone P, McCormick SA, Walsh J (2009) Urinary 6-sulfatoxymelatonin level in age-related macular degeneration patients. Mol Vis 15:1673-1679.
130. Schmid-Kubista KE, Glittenberg CG, Cezanne M, Holzmann K, Neumaier-Ammerer B, Binder S (2009) Daytime levels of melatonin in patients with age-related macular degeneration. Acta Ophthalmol 87(1):89-93. doi: AOS1173 [pii] 10.1111/j.1755-3768.2008.01173.x.
131. Prashar S, Pandav SS, Gupta A, Nath R (1993) Antioxidant enzymes in RBCs as a biological index of age related macular degeneration. Acta Ophthalmol (Copenh) 71(2):214-218.
132. Delcourt C, Cristol JP, Leger CL, Descomps B, Papoz L (1999) Associations of antioxidant enzymes with cataract and age-related macular degeneration. The POLA Study. Pathologies Oculaires Liees a l'Age. Ophthalmology 106(2):215-222.
133. De La Paz MA, Zhang J, Fridovich I (1996) Red blood cell antioxidant enzymes in agerelated macular degeneration. Br J Ophthalmol 80(5):445-450.
134. Cohen SM, Olin KL, Feuer WJ, Hjelmeland L, Keen CL, Morse LS (1994) Low glutathione reductase and peroxidase activity in age-related macular degeneration. Br J Ophthalmol 78(10):791-794.
135. Baskol G, Karakucuk S, Oner AO, Baskol M, Kocer D, Mirza E, Saraymen R, Ustdal M (2006) Serum paraoxonase 1 activity and lipid peroxidation levels in patients with age-related macular degeneration. Ophthalmologica 220(1):12-16. doi: OPH2006220001012 [pii] 10.1159/000089269.
136. Kimura K, Isashiki Y, Sonoda S, Kakiuchi-Matsumoto T, Ohba N (2000) Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. Am J Ophthalmol 130(6):769-773. doi: S0002939400005523 [pii].
137. Gotoh N, Yamada R, Matsuda F, Yoshimura N, Iida T (2008) Manganese superoxide dismutase gene (SOD2) polymorphism and exudative age-related macular degeneration in the Japanese population. Am J Ophthalmol 146(1):146; author reply 146-147. doi: S0002-9394(08)00219-5 [pii] 10.1016/j.ajo.2008.03.017.
138. Kondo N, Bessho H, Honda S, Negi A (2009) SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Mol Vis 15:1819-1826.
139. Esfandiary H, Chakravarthy U, Patterson C, Young I, Hughes AE (2005) Association study of detoxification genes in age related macular degeneration. Br J Ophthalmol 89(4):470-474. doi: 89/4/470 [pii] 10.1136/bjo.2004.047340.
140. Kowalski M, Bielecka-Kowalska A, Oszajca K, Makandjou-Ola E, Jaworski P, Bartkowiak J, Szemraj J (2010) Manganese superoxide dismutase (MnSOD) gene (Ala-9Val, Ile58Thr) polymorphism in patients with age-related macular degeneration (AMD). Med Sci Monit 16(4):CR190-CR196. doi: 878501 [pii].
141. Pauer GJ, Sturgill GM, Peachey NS, Hagstrom SA (2010) Protective effect of paraoxonase 1 gene variant Gln192Arg in age-related macular degeneration. Am J Ophthalmol 149(3):513-522. doi: S0002-9394(09)00737-5 [pii] 10.1016/j.ajo.2009.09.024.
142. Baird PN, Chu D, Guida E, Vu HT, Guymer R (2004) Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration. Am J Ophthalmol 138(4):665-666. doi: S0002-9394(04)00491-X [pii] 10.1016/j.ajo.2004.04.053.
143. Haas P, Aggermann T, Steindl K, Krugluger W, Puhringer H, Oberkanins C, Frantal S, Binder S (2011) Genetic cardiovascular risk factors and age-related macular degeneration. Acta Ophthalmol 89(4):335-8. doi: AOS1697 [pii] 10.1111/j.1755-3768.2009.01697.x.
144. Ayala-Haedo JA, Gallins PJ, Whitehead PL, Schwartz SG, Kovach JL, Postel EA, Agarwal A, Wang G, Haines JL, Pericak-Vance MA, Scott WK (2010) Analysis of single nucleotide polymorphisms in the NOS2A gene and interaction with smoking in agerelated macular degeneration. Ann Hum Genet 74(3):195-201. doi: AHG570 [pii] 10.1111/j.1469-1809.2010.00570.x.
145. Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283(5407):1482-1488.
146. Torroni A, Huoponen K, Francalacci P, Petrozzi M, Morelli L, Scozzari R, Obinu D, Savontaus ML, Wallace DC (1996) Classification of European mtDNAs from an analysis of three European populations. Genetics 144(4):1835-1850.
147. Jones MM, Manwaring N, Wang JJ, Rochtchina E, Mitchell P, Sue CM (2007) Mitochondrial DNA haplogroups and age-related maculopathy. Arch Ophthalmol 125(9):1235-1240. doi: 125/9/1235 [pii] 10.1001/archopht.125.9.1235.
148. SanGiovanni JP, Arking DE, Iyengar SK, Elashoff M, Clemons TE, Reed GF, Henning AK, Sivakumaran TA, Xu X, DeWan A, Agron E, Rochtchina E, Sue CM, Wang JJ, Mitchell P, Hoh J, Francis PJ, Klein ML, Chew EY, Chakravarti A (2009) Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration. PLoS One 4(5):e5508. doi: 10.1371/journal. pone.0005508.
149. Canter JA, Olson LM, Spencer K, Schnetz-Boutaud N, Anderson B, Hauser MA, Schmidt S, Postel EA, Agarwal A, Pericak-Vance MA, Sternberg P Jr, Haines JL (2008) Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration. PLoS One 3(5):e2091. doi: 10.1371/journal.pone.0002091.
150. Udar N, Atilano SR, Memarzadeh M, Boyer DS, Chwa M, Lu S, Maguen B, Langberg J, Coskun P, Wallace DC, Nesburn AB, Khatibi N, Hertzog D, Le K, Hwang D, Kenney MC (2009) Mitochondrial DNA haplogroups associated with age-related macular degeneration. Invest Ophthalmol Vis Sci 50(6):2966-2974. doi: iovs.08-2646 [pii] 10.1167/iovs.08-2646.
151. Fritsche LG, Loenhardt T, Janssen A, Fisher SA, Rivera A, Keilhauer CN, Weber BH (2008) Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet 40(7):892-896. doi: ng.170 [pii] 10.1038/ng.170.
152. Schmidt S, Hauser MA, Scott WK, Postel EA, Agarwal A, Gallins P, Wong F, Chen YS, Spencer K, Schnetz-Boutaud N, Haines JL, Pericak-Vance MA (2006) Cigarette smoking strongly modifies the association of LOC387715 and age-related macular degeneration. Am J Hum Genet 78(5):852-864. doi: S0002-9297(07)63818-X [pii] 10.1086/503822.
153. Schaumberg DA, Hankinson SE, Guo Q, Rimm E, Hunter DJ (2007) A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. Arch Ophthalmol 125(1):55-62. doi: 125/1/55 [pii] 10.1001/archopht.125.1.55.
154. Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP (2005) Smoking and age-related macular degeneration: a review of association. Eye (Lond) 19(9):935-944. doi: 6701978 [pii] 10.1038/sj.eye.6701978.
155. Cong R, Zhou B, Sun Q, Gu H, Tang N, Wang B (2008) Smoking and the risk of age-related macular degeneration: a meta-analysis. Ann Epidemiol 18(8):647-656. doi: S1047-2797(08)00090-2 [pii] 10.1016/j.annepidem.2008.04.002.
156. Neuner B, Komm A, Wellmann J, Dietzel M, Pauleikhoff D, Walter J, Busch M, Hense HW (2009) Smoking history and the incidence of age-related macular degeneration-results from the Muenster Aging and Retina Study (MARS) cohort and systematic review and meta-analysis of observational longitudinal studies. Addict Behav 34(11):938-947. doi: S0306-4603(09)00140-3 [pii] 10.1016/j.addbeh.2009.05.015.
157. Moriarty SE, Shah JH, Lynn M, Jiang S, Openo K, Jones DP, Sternberg P (2003) Oxidation of glutathione and cysteine in human plasma associated with smoking. Free Radic Biol Med 35(12):1582-1588. doi: S0891584903005987 [pii].
158. Sobczak A, Wardas W, Zielinska-Danch W, Pawlicki K (2004) The influence of smoking on plasma homocysteine and cysteine levels in passive and active smokers. Clin Chem Lab Med 42(4):408-414. doi: 10.1515/CCLM.2004.072.
159. Neuner B, Wellmann J, Dasch B, Dietzel M, Farwick A, Stoll M, Pauleikhoff D, Hense HW (2008) LOC387715, smoking and their prognostic impact on visual functional status in agerelated macular degeneration-The Muenster Aging and Retina Study (MARS) cohort. Ophthalmic Epidemiol 15(3):148-154. doi: 794321328 [pii] 10.1080/09286580802105830.
160. Nakanishi H, Yamashiro K, Yamada R, Gotoh N, Hayashi H, Nakata I, Saito M, Iida T, Oishi A, Kurimoto Y, Matsuo K, Tajima K, Matsuda F, Yoshimura N (2010) Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci 51(12):6183-6187. doi: iovs.09-4948 [pii] 10.1167/ iovs.09-4948.
161. DeAngelis MM, Ji F, Kim IK, Adams S, Capone A Jr, Ott J, Miller JW, Dryja TP (2007) Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration. Arch Ophthalmol 125(1):49-54. doi: 125/1/49 [pii] 10.1001/archopht.125.1.49.
162. West SK, Rosenthal FS, Bressler NM, Bressler SB, Munoz B, Fine SL, Taylor HR (1989) Exposure to sunlight and other risk factors for age-related macular degeneration. Arch Ophthalmol 107(6):875-879.
163. Taylor HR, West S, Munoz B, Rosenthal FS, Bressler SB, Bressler NM (1992) The long-term effects of visible light on the eye. Arch Ophthalmol 110(1):99-104.
164. Darzins P, Mitchell P, Heller RF (1997) Sun exposure and age-related macular degeneration. An Australian case-control study. Ophthalmology 104(5):770-776.
165. Mitchell P, Smith W, Wang JJ (1998) Iris color, skin sun sensitivity, and age-related maculopathy. The Blue Mountains Eye Study. Ophthalmology 105(8):1359-1363. doi: S0161-6420(98)98013-7 [pii] 10.1016/S0161-6420(98)98013-7.
166. Khan JC, Shahid H, Thurlby DA, Bradley M, Clayton DG, Moore AT, Bird AC, Yates JR (2006) Age related macular degeneration and sun exposure, iris colour, and skin sensitivity to sunlight. Br J Ophthalmol 90(1):29-32. doi: 90/1/29 [pii] 10.1136/bjo.2005.073825.
167. Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, de Jong PT, Rahu M, Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Vioque J (2008) Sunlight exposure, antioxidants, and age-related macular degeneration. Arch Ophthalmol 126(10):1396-1403. doi: 126/10/1396 [pii] 10.1001/archopht.126.10.1396.
168. Evans J (2008) Antioxidant supplements to prevent or slow down the progression of AMD: a systematic review and meta-analysis. Eye (Lond) 22(6):751-760. doi: eye2008100 [pii] 10.1038/eye.2008.100.
169. Krishnadev N, Meleth AD, Chew EY (2010) Nutritional supplements for age-related macular degeneration. Curr Opin Ophthalmol 21(3):184-189. doi: 10.1097/ICU.0b013e32833866ee.
170. Moriarty-Craige SE, Adkison J, Lynn M, Gensler G, Bressler S, Jones DP, Sternberg P Jr (2005) Antioxidant supplements prevent oxidation of cysteine/cystine redox in patients with age-related macular degeneration. Am J Ophthalmol 140(6):1020-1026. doi: S0002-9394(05)00725-7 [pii] 10.1016/j.ajo.2005.06.043.
171. Moriarty-Craige SE, Ha KN, Sternberg P Jr, Lynn M, Bressler S, Gensler G, Jones DP (2007) Effects of long-term zinc supplementation on plasma thiol metabolites and redox status in patients with age-related macular degeneration. Am J Ophthalmol 143(2):206-211. doi: S0002-9394(06)01133-0 [pii] 10.1016/j.ajo.2006.09.056.
172. Cangemi FE (2007) TOZAL Study: an open case control study of an oral antioxidant and omega-3 supplement for dry AMD. BMC Ophthalmol 7:3. doi: 1471-2415-7-3 [pii] 10.1186/1471-2415-7-3.
173. Parisi V, Tedeschi M, Gallinaro G, Varano M, Saviano S, Piermarocchi S (2008) Carotenoids and antioxidants in age-related maculopathy italian study: multifocal electroretinogram modifications after 1 year. Ophthalmology 115(2):324-333 e322. doi: S0161-6420(07)00581-7 [pii] 10.1016/j.ophtha.2007.05.029.
174. Patel M, Chan CC (2008) Immunopathological aspects of age-related macular degeneration. Semin Immunopathol 30(2):97-110. doi: 10.1007/s00281-008-0112-9.
175. Chen M, Forrester JV, Xu H (2007) Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments. Exp Eye Res 84(4):635-645. doi: S0014-4835(06)00457-X [pii] 10.1016/j.exer.2006.11.015.
176. Wu Z, Lauer TW, Sick A, Hackett SF, Campochiaro PA (2007) Oxidative stress modulates complement factor H expression in retinal pigmented epithelial cells by acetylation of FOXO3. J Biol Chem 282(31):22414-22425. doi: M702321200 [pii] 10.1074/jbc. M702321200.
177. Thurman JM, Renner B, Kunchithapautham K, Ferreira VP, Pangburn MK, Ablonczy Z, Tomlinson S, Holers VM, Rohrer B (2009) Oxidative stress renders retinal pigment epithelial cells susceptible to complement-mediated injury. J Biol Chem 284(25):16939-16947. doi: M808166200 [pii] 10.1074/jbc.M808166200.
178. Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L, Ufret RL, Salomon RG, Perez VL (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med 14(2):194-198. doi: nm1709 [pii] 10.1038/nm1709.