Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors

Eye and Vision

Volumn 3, Issue 1, 2016, Pages

  Pennington, Katie L ^a   DeAngelis, Margaret M ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Antioxidants; Atherosclerosis; BMI; Cholesterol; Genetic association; Hypertension; Obesity; Retina; Statins; Stroke

Indexed keywords

EID: 85090484362     PISSN: None     EISSN: 23260254     Source Type: Journal    
DOI: 10.1186/s40662-016-0063-5     Document Type: Review

References (225)

1. Sources for Macular Degeneration: Facts & Figures [http://www.brightfocus.org/sources-macular-degeneration-facts-figures]. Accessed 28 Oct 2015.
2. Wong WL, Su X, Li X, Cheung CMG, 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:e106–16. DOI: 10.1016/S2214-109X(13)70145-1
3. Pascolini D, Mariotti SP. Global estimates of visual impairment: 2010. Br J Ophthalmol. 2012;96:614–8. DOI: 10.1136/bjophthalmol-2011-300539
4. About Alzheimer’s Disease: Alzheimer’s Basics [https://www.nia.nih.gov/alzheimers/topics/alzheimers-basics]. Accessed 9 Nov 2015.
5. Cost of Vision Problems — Medical Costs by Disorder [http://costofvision.preventblindness.org/costs/direct-costs/medical-costs-by-disorder]. Accessed 9 Nov 2015.
6. Curcio CA, Medeiros NE, Millican CL. Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1996;37:1236–49.
7. Klein R, Klein BEK, Jensen SC, Meuer SM. The Five-year Incidence and Progression of Age-related Maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997;104:7–21. DOI: 10.1016/S0161-6420(97)30368-6
8. Age-Related Eye Disease Study Research Group. The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the Age-Related Eye Disease Study Report Number 6. Am J Ophthalmol. 2001;132:668–81. DOI: 10.1016/S0002-9394(01)01218-1
9. Shah AR, Del Priore LV. Progressive Visual Loss in Subfoveal Exudation in Age-related Macular Degeneration: A Meta-analysis Using Lineweaver-Burke Plots. Am J Ophthalmol. 2007;143:83–9. e2. DOI: 10.1016/j.ajo.2006.09.043
10. Ferris 3rd FL, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102:1640–2. DOI: 10.1001/archopht.1984.01040031330019
11. Cook HL, Patel PJ, Tufail A. Age-related macular degeneration: diagnosis and management. Br Med Bull. 2008;85:127–49. DOI: 10.1093/bmb/ldn012
12. Ferris FL, Davis MD, Clemons TE, Lee LY, Chew EY, Lindblad AS, Milton RC, Bressler SB, Klein R, Age-Related Eye Disease Study Research Group. A Simplified Severity Scale for Age-Related Macular Degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005;123:1570–4. DOI: 10.1001/archopht.123.11.1570
13. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008;358:2606–17. DOI: 10.1056/NEJMra0801537
14. 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;119:1417–36. DOI: 10.1001/archopht.119.10.1417
15. Davis MD, Gangnon RE, Lee L-Y, Hubbard LD, Klein BEK, Klein R, Ferris FL, Bressler SB, Milton RC, Age-Related Eye Disease Study Group. The Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration: AREDS Report No. 17. Arch Ophthalmol. 2005;123:1484–98. DOI: 10.1001/archopht.123.11.1484
16. Khan KN, Mahroo OA, Khan RS, Mohamed MD, McKibbin M, Bird A, et al. Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes. Prog Retin Eye Res. 2016;53:70–106. DOI: 10.1016/j.preteyeres.2016.04.008
17. Mitchell P, Korobelnik JF, Lanzetta P, Holz FG, Prünte C, Schmidt-Erfurth U, et al. Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials. Br J Ophthalmol. 2010;94:2–13. DOI: 10.1136/bjo.2009.159160
18. Amoaku WM, Chakravarthy U, Gale R, Gavin M, Ghanchi F, Gibson J, et al. Defining response to anti-VEGF therapies in neovascular AMD. Eye (Lond). 2015;29:721–31. DOI: 10.1038/eye.2015.48
19. Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J. Forecasting Age-Related Macular Degeneration Through the Year 2050: The Potential Impact of New Treatments. Arch Ophthalmol. 2009;127:533–40. DOI: 10.1001/archophthalmol.2009.58
20. Querques G, Rosenfeld PJ, Cavallero E, Borrelli E, Corvi F, Querques L, et al. Treatment of dry age-related macular degeneration. Ophthalmic Res. 2014;52:107–15. DOI: 10.1159/000363187
21. Nowak JZ. AMD--the retinal disease with an unprecised etiopathogenesis: in search of effective therapeutics. Acta Pol Pharm. 2014;71:900–16.
22. Morgan DJ, DeAngelis MM. Differential Gene Expression in Age-Related Macular Degeneration. Cold Spring Harb Perspect Med. 2015;5:a017210. DOI: 10.1101/cshperspect.a017210
23. Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A. Age-related macular degeneration: genetics and biology coming together. Annu Rev Genomics Hum Genet. 2014;15:151–71. DOI: 10.1146/annurev-genom-090413-025610
24. Fritsche LG, Igl W, Bailey JNC, Grassmann F, Sengupta S, Bragg-Gresham JL, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016;48(2):134–43. DOI: 10.1038/ng.3448
25. Pennington KL, DeAngelis MM. Epigenetic Mechanisms of the Aging Human Retina. J Exp Neurosci. 2015;9 Suppl 2:51–79.
26. Armstrong RA, Mousavi M. Overview of Risk Factors for Age-Related Macular Degeneration (AMD). J Stem Cells. 2015;10:171–91.
27. Gemenetzi M, Lotery AJ. The role of epigenetics in age-related macular degeneration. Eye (Lond). 2014;28:1407–17. DOI: 10.1038/eye.2014.225
28. Zhang QY, Tie LJ, Wu SS, Lv PL, Huang HW, Wang WQ, et al. Overweight, Obesity, and Risk of Age-Related Macular Degeneration. Invest Opthalmol Vis Sci. 2016;57:1276–83. DOI: 10.1167/iovs.15-18637
29. Handa JT, Cano M, Wang L, Datta S, Liu T. Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related MacularDegeneration. Biochim Biophys Acta. 2016. doi:10.1016/j.bbalip.2016.07.013 [Epub ahead of print].
30. Black JRM, Clark SJ. Age-related macular degeneration: genome-wide association studies to translation. Genet Med. 2016;18(4):283–9. DOI: 10.1038/gim.2015.70
31. Chen M, Xu H. Parainflammation, chronic inflammation, and age-related macular degeneration. J Leukoc Biol. 2015;98:713–25. DOI: 10.1189/jlb.3RI0615-239R
32. Knickelbein JE, Chan CC, Sen HN, Ferris FL, Nussenblatt RB. Inflammatory Mechanisms of Age-related Macular Degeneration. Int Ophthalmol Clin. 2015;55:63–78. DOI: 10.1097/IIO.0000000000000073
33. van Lookeren CM, Strauss EC, Yaspan BL. Age-related macular degeneration: Complement in action. Immunobiology. 2016;221:733–9. DOI: 10.1016/j.imbio.2015.11.007
34. Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci. 2016;73:1765–86. DOI: 10.1007/s00018-016-2147-8
35. Lambert NG, ElShelmani H, Singh MK, Mansergh FC, Wride MA, Padilla M, et al. Risk factors and biomarkers of age-related macular degeneration. Prog Retin Eye Res. 2016;54:64–102. DOI: 10.1016/j.preteyeres.2016.04.003
36. Tan PL, Bowes Rickman C, Katsanis N. AMD and the alternative complement pathway: genetics and functional implications. Hum Genomics. 2016;10:23. DOI: 10.1186/s40246-016-0079-x
37. Gelfand BD, Ambati J. A Revised Hemodynamic Theory of Age-Related Macular Degeneration. Trends Mol Med. 2016;22:656–70. DOI: 10.1016/j.molmed.2016.06.009
38. Schwartz SG, Hampton BM, Kovach JL, Brantley Jr MA. Genetics and age-related macular degeneration: a practical review for the clinician. Clin Ophthalmol. 2016;10:1229–35. DOI: 10.2147/OPTH.S109723
39. Riaz M, Baird PN. Genetics in Retinal Diseases. Dev Ophthalmol. 2016;55:57–62. DOI: 10.1159/000431142
40. Stefánsson E, Geirsdóttir A, Sigurdsson H. Metabolic physiology in age related macular degeneration. Prog Retin Eye Res. 2011;30:72–80. DOI: 10.1016/j.preteyeres.2010.09.003
41. Gemenetzi M, Lotery AJ. Complement pathway biomarkers and age-related macular degeneration. Eye (Lond). 2016;30(1):1–14. DOI: 10.1038/eye.2015.203
42. Stanton CM, Wright AF. Inflammatory biomarkers for AMD. Adv Exp Med Biol. 2014;801:251–7. DOI: 10.1007/978-1-4614-3209-8_32
43. Parmeggiani F, Romano MR, Costagliola C, Semeraro F, Incorvaia C, D’Angelo S, et al. Mechanism of inflammation in age-related macular degeneration. Mediators Inflamm. 2012;2012:546786. DOI: 10.1155/2012/546786
44. Blasiak J, Petrovski G, Veréb Z, Facskó A, Kaarniranta K. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration. Biomed Res Int. 2014;2014:768026. DOI: 10.1155/2014/768026
45. Pikuleva IA, Curcio CA. Cholesterol in the retina: the best is yet to come. Prog Retin Eye Res. 2014;41:64–89. DOI: 10.1016/j.preteyeres.2014.03.002
46. Fliesler SJ, Bretillon L. The ins and outs of cholesterol in the vertebrate retina. J Lipid Res. 2010;51:3399–413. DOI: 10.1194/jlr.R010538
47. Machalińska A, Kawa MP, Marlicz W, Machaliński B. Complement system activation and endothelial dysfunction in patients with age-related macular degeneration (AMD): possible relationship between AMD and atherosclerosis. Acta Ophthalmol. 2012;90:695–703. DOI: 10.1111/j.1755-3768.2011.02295.x
48. Logue MW, Schu M, Vardarajan BN, Farrell J, Lunetta KL, Jun G, et al. Search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways. Neurobiol Aging. 2014;35:1510. e7-18. DOI: 10.1016/j.neurobiolaging.2013.12.007
49. Silveira AC, Morrison MA, Ji F, Xu H, Reinecke JB, Adams SM, et al. Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: a systems biology based approach. Vision Res. 2010;50:698–715. DOI: 10.1016/j.visres.2009.09.016
50. Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, et al. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci U S A. 2010;107:7401–6. DOI: 10.1073/pnas.0912702107
51. Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, Raychaudhuri S, et al. Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci U S A. 2010;107:7395–400. DOI: 10.1073/pnas.0912019107
52. Restrepo NA, Spencer KL, Goodloe R, Garrett TA, Heiss G, Bůžková P, et al. Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study. Invest Ophthalmol Vis Sci. 2014;55:6839–50. DOI: 10.1167/iovs.14-14246
53. Klein R, Myers CE, Buitendijk GH, Rochtchina E, Gao X, de Jong PT, et al. Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium. Am J Ophthalmol. 2014;158:513–24. e3. DOI: 10.1016/j.ajo.2014.05.027
54. Ferris FL, Davis MD, Clemons TE, Lee LY, Chew EY, Lindblad AS, et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005;123:1570–4. DOI: 10.1001/archopht.123.11.1570
55. Mullins RF, Russell SR, Anderson DH, Hageman GS. 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. 2000;14:835–46.
56. Booij JC, Baas DC, Beisekeeva J, Gorgels TG, Bergen AA. The dynamic nature of Bruch’s membrane. Prog Retin Eye Res. 2010;29:1–18. DOI: 10.1016/j.preteyeres.2009.08.003
57. Friedman E. A hemodynamic model of the pathogenesis of age-related macular degeneration. Am J Ophthalmol. 1997;124:677–82. DOI: 10.1016/S0002-9394(14)70906-7
58. Friedman E. The role of the atherosclerotic process in the pathogenesis of age-related macular degeneration. Am J Ophthalmol. 2000;130:658–63. DOI: 10.1016/S0002-9394(00)00643-7
59. Friedman E. Update of the vascular model of AMD. Br J Ophthalmol. 2004;88:161–3. DOI: 10.1136/bjo.2003.036277
60. Friedman E. The pathogenesis of age-related macular degeneration. Am J Ophthalmol. 2008;146:348–9. DOI: 10.1016/j.ajo.2008.05.017
61. Vitale S, Clemons TE, Agrón E, Ferris 3rd FL, Domalpally A, Danis RP, et al. Evaluating the Validity of the Age-Related Eye Disease Study Grading Scale for Age-Related Macular Degeneration: AREDS2 Report 10. JAMA Ophthalmol. 2016;134:1041–7. DOI: 10.1001/jamaophthalmol.2016.2383
62. Grassmann F, Fleckenstein M, Chew EY, Strunz T, Schmitz-Valckenberg S, Göbel AP, et al. Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration. PLoS One. 2015;10:e0126636. DOI: 10.1371/journal.pone.0126636
63. Varma R, Foong AW, Lai MY, Choudhury F, Klein R, Azen SP, et al. Four-year incidence and progression of age-related macular degeneration: the Los Angeles Latino Eye Study. Am J Ophthalmol. 2010;149:741–51. DOI: 10.1016/j.ajo.2010.01.009
64. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317–25. DOI: 10.1038/nature10146
65. Klein R, Chou CF, Klein BE, Zhang X, Meuer SM, Saaddine JB. Prevalence of age-related macular degeneration in the US population. Arch Ophthalmol. 2011;129:75–80. DOI: 10.1001/archophthalmol.2010.318
66. Souied EH, Benlian P, Amouyel P, Feingold J, Lagarde JP, Munnich A, et al. The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration. Am J Ophthalmol. 1998;125:353–9. DOI: 10.1016/S0002-9394(99)80146-9
67. Klaver CC, Kliffen M, van Duijn CM, Hofman A, Cruts M, Grobbee DE, et al. Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet. 1998;63:200–6. DOI: 10.1086/301901
68. Fritsche LG, Chen W, Schu M, Yaspan BL, Yu Y, Thorleifsson G, et al. Seven new loci associated with age-related macular degeneration. Nat Genet. 2013;45:433–9. DOI: 10.1038/ng.2578
69. Zareparsi S, Buraczynska M, Branham KE, Shah S, Eng D, Li M, et al. Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. Hum Mol Genet. 2005;14:1449–55. DOI: 10.1093/hmg/ddi154
70. Hussain AA, Lee Y, Zhang JJ, Marshall J. Disturbed matrix metalloproteinase activity of Bruch’s membrane in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52:4459–66. DOI: 10.1167/iovs.10-6678
71. McKay GJ, Patterson CC, Chakravarthy U, Dasari S, Klaver CC, Vingerling JR, et al. Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies. Hum Mutat. 2011;32:1407–16. DOI: 10.1002/humu.21577
72. Reynolds R, Rosner B, Seddon JM. Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. Ophthalmology. 2010;117:1989–95. DOI: 10.1016/j.ophtha.2010.07.009
73. Yu Y, Reynolds R, Fagerness J, Rosner B, Daly MJ, Seddon JM. Association of variants in the LIPC and ABCA1 genes with intermediate and large drusen and advanced age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52:4663–70. DOI: 10.1167/iovs.10-7070
74. Liu K, Chen LJ, Lai TY, Tam PO, Ho M, Chiang SW, et al. Genes in the high-density lipoprotein metabolic pathway in age-related macular degeneration and polypoidal choroidal vasculopathy. Ophthalmology. 2014;121:911–6. DOI: 10.1016/j.ophtha.2013.10.042
75. Wang D, Zhou J, Hou X, Nguyen DH, Cao G, Li G, et al. CETP Gene may be Associated with Advanced Age-Related Macular Degeneration in the Chinese Population. Ophthalmic Genet. 2015;36:303–8. DOI: 10.3109/13816810.2014.881506
76. Wang YF, Han Y, Zhang R, Qin L, Wang MX, Ma L. CETP/LPL/LIPC gene polymorphisms and susceptibility to age-related macular degeneration. Sci Rep. 2015;5:15711. DOI: 10.1038/srep15711
77. Fauser S, Smailhodzic D, Caramoy A, van de Ven JP, Kirchhof B, Hoyng CB, et al. Evaluation of serum lipid concentrations and genetic variants at high-density lipoprotein metabolism loci and TIMP3 in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52:5525–8. DOI: 10.1167/iovs.10-6827
78. Jun G, Nicolaou M, Morrison MA, Buros J, Morgan DJ, Radeke MJ, et al. Influence of ROBO1 and RORA on risk of age-related macular degeneration reveals genetically distinct phenotypes in disease pathophysiology. PLoS One. 2011;6:e25775. DOI: 10.1371/journal.pone.0025775
79. Schaumberg DA, Chasman D, Morrison MA, Adams SM, Guo Q, Hunter DJ, et al. Prospective study of common variants in the retinoic acid receptor-related orphan receptor α gene and risk of neovascular age-related macular degeneration. Arch Ophthalmol. 2010;128:1462–71. DOI: 10.1001/archophthalmol.2010.261
80. Kloeckener-Gruissem B, Barthelmes D, Labs S, Schindler C, Kurz-Levin M, Michels S, et al. Genetic association with response to intravitreal ranibizumab in patients with neovascular AMD. Invest Ophthalmol Vis Sci. 2011;52:4694–702. DOI: 10.1167/iovs.10-6080
81. Haines JL, Schnetz-Boutaud N, Schmidt S, Scott WK, Agarwal A, Postel EA, et al. Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6. Invest Ophthalmol Vis Sci. 2006;47:329–35. DOI: 10.1167/iovs.05-0116
82. Kaarniranta K, Paananen J, Nevalainen T, Sorri I, Seitsonen S, Immonen I, et al. Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age-related macular degeneration in Finnish population. Neurosci Lett. 2012;513:233–7. DOI: 10.1016/j.neulet.2012.02.050
83. Lechanteur YT, van de Ven JP, Smailhodzic D, Boon CJ, Klevering BJ, Fauser S, et al. Genetic, behavioral, and sociodemographic risk factors for second eye progression in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2012;53:5846–52. DOI: 10.1167/iovs.11-7731
84. Merle BM, Maubaret C, Korobelnik JF, Delyfer MN, Rougier MB, Lambert JC, et al. Association of HDL-related loci with age-related macular degeneration and plasma lutein and zeaxanthin: the Alienor study. PLoS One. 2013;8:e79848. DOI: 10.1371/journal.pone.0079848
85. Sun Y, Liu CH, SanGiovanni JP, Evans LP, Tian KT, Zhang B, et al. Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation. Proc Natl Acad Sci U S A. 2015;112:10401–6. DOI: 10.1073/pnas.1504387112
86. Gorin MB. Genetic insights into age-related macular degeneration: controversies addressing risk, causality, and therapeutics. Mol Aspects Med. 2012;33:467–86. DOI: 10.1016/j.mam.2012.04.004
87. Joyce C, Freeman L, Brewer HB, Santamarina-Fojo S. Study of ABCA1 function in transgenic mice. Arterioscler Thromb Vasc Biol. 2003;23:965–71. DOI: 10.1161/01.ATV.0000055194.85073.FF
88. Sene A, Khan AA, Cox D, Nakamura RE, Santeford A, Kim BM, et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab. 2013;17:549–61. DOI: 10.1016/j.cmet.2013.03.009
89. Guay SP, Brisson D, Munger J, Lamarche B, Gaudet D, Bouchard L. ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia. Epigenetics. 2012;7:464–72. DOI: 10.4161/epi.19633
90. Guay SP, Légaré C, Houde AA, Mathieu P, Bossé Y, Bouchard L. Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men. Clin Epigenetics. 2014;6:14. DOI: 10.1186/1868-7083-6-14
91. Hafiane A, Bielicki JK, Johansson JO, Genest J. Novel Apo E-Derived ABCA1 Agonist Peptide (CS-6253) Promotes Reverse Cholesterol Transport and Induces Formation of preβ-1 HDL In Vitro. PLoS One. 2015;10:e0131997. DOI: 10.1371/journal.pone.0131997
92. Cheng CY, Yamashiro K, Chen LJ, Ahn J, Huang L, Huang L, et al. New loci and coding variants confer risk for age-related macular degeneration in East Asians. Nat Commun. 2015;6:6063. DOI: 10.1038/ncomms7063
93. Orsó E, Broccardo C, Kaminski WE, Böttcher A, Liebisch G, Drobnik W, et al. Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice. Nat Genet. 2000;24:192–6. DOI: 10.1038/72869
94. Chang HS, Lin CH, Chen YC, Yu WC. Using siRNA technique to generate transgenic animals with spatiotemporal and conditional gene knockdown. Am J Pathol. 2004;165:1535–41. DOI: 10.1016/S0002-9440(10)63411-6
95. Qiu Y, Cavelier L, Chiu S, Yang X, Rubin E, Cheng JF. Human and mouse ABCA1 comparative sequencing and transgenesis studies revealing novel regulatory sequences. Genomics. 2001;73:66–76. DOI: 10.1006/geno.2000.6467
96. Kim WS, Fitzgerald ML, Kang K, Okuhira K, Bell SA, Manning JJ, et al. Abca7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels. J Biol Chem. 2005;280:3989–95. DOI: 10.1074/jbc.M412602200
97. Smith JD, Plump AS, Hayek T, Walsh A, Breslow JL. Accumulation of human apolipoprotein E in the plasma of transgenic mice. J Biol Chem. 1990;265:14709–12.
98. Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 1992;258:468–71. DOI: 10.1126/science.1411543
99. Agellon LB, Walsh A, Hayek T, Moulin P, Jiang XC, Shelanski SA, et al. Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. J Biol Chem. 1991;266:10796–801.
100. Warden CH, Fisler JS, Shoemaker SM, Wen PZ, Svenson KL, Pace MJ, et al. Identification of four chromosomal loci determining obesity in a multifactorial mouse model. J Clin Invest. 1995;95:1545–52. DOI: 10.1172/JCI117827
101. Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, et al. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell. 1998;93:411–22. DOI: 10.1016/S0092-8674(00)81169-1
102. Albers JJ, Tu AY, Paigen B, Chen H, Cheung MC, Marcovina SM. Transgenic mice expressing human phospholipid transfer protein have increased HDL/non-HDL cholesterol ratio. Int J Clin Lab Res. 1996;26:262–7. DOI: 10.1007/BF02602960
103. Jiang XC, Bruce C, Mar J, Lin M, Ji Y, Francone OL, et al. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J Clin Invest. 1999;103:907–14. DOI: 10.1172/JCI5578
104. Kahn HA, Leibowitz HM, Ganley JP, Kini MM, Colton T, Nickerson RS, et al. The Framingham Eye Study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study. Am J Epidemiol. 1977;106:33–41.
105. Woodell A, Rohrer B. A mechanistic review of cigarette smoke and age-related macular degeneration. Adv Exp Med Biol. 2014;801:301–7. DOI: 10.1007/978-1-4614-3209-8_38
106. Rastogi N, Smith RT. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease. Surv Ophthalmol. 2016;61:422–33. DOI: 10.1016/j.survophthal.2015.10.003
107. Risk factors for neovascular age-related macular degeneration. The Eye Disease Case–control Study Group. Arch Ophthalmol. 1992;110:1701–8.
108. Klein R, Klein BE, Franke T. The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1993;100:406–14. DOI: 10.1016/S0161-6420(93)31634-9
109. Klein R, Klein BE, Tomany SC, Cruickshanks KJ. The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 2003;110:1273–80. DOI: 10.1016/S0161-6420(03)00599-2
110. Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al. Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology. 2001;108:697–704. DOI: 10.1016/S0161-6420(00)00580-7
111. Tomany SC, Wang JJ, Van Leeuwen R, Klein R, Mitchell P, Vingerling JR, et al. Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology. 2004;111:1280–7. DOI: 10.1016/j.ophtha.2003.11.010
112. Klein R, Deng Y, Klein BE, Hyman L, Seddon J, Frank RN, et al. Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women’s Health Initiative Sight Exam ancillary study. Am J Ophthalmol. 2007;143:473–83. DOI: 10.1016/j.ajo.2006.11.058
113. Fraser-Bell S, Wu J, Klein R, Azen SP, Hooper C, Foong AW, et al. Cardiovascular risk factors and age-related macular degeneration: the Los Angeles Latino Eye Study. Am J Ophthalmol. 2008;145:308–16. DOI: 10.1016/j.ajo.2007.10.007
114. Golan S, Shalev V, Goldstein M, Treister G, Chodick G, Loewenstein A. The rate of myocardial infarction events among patients with age-related macular degeneration: a population-based study. Graefes Arch Clin Exp Ophthalmol. 2011;249:179–82. DOI: 10.1007/s00417-010-1489-4
115. Erke MG, Bertelsen G, Peto T, Sjølie AK, Lindekleiv H, Njølstad I. Cardiovascular risk factors associated with age-related macular degeneration: the Tromsø Study. Acta Ophthalmol. 2014;92:662–9. DOI: 10.1111/aos.12346
116. Hyman LG, Lilienfeld AM, Ferris 3rd FL, Fine SL. Senile macular degeneration: a case–control study. Am J Epidemiol. 1983;118:213–27.
117. Tan JS, Mitchell P, Smith W, Wang JJ. Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology. 2007;114:1143–50. DOI: 10.1016/j.ophtha.2006.09.033
118. Clemons TE, Kurinij N, Sperduto RD, AREDS Research Group. Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13. Arch Ophthalmol. 2004;122:716–26. DOI: 10.1001/archopht.122.5.716
119. Vassilev ZP, Ruigómez A, Soriano-Gabarró M, García Rodríguez LA. Diabetes, cardiovascular morbidity, and risk of age-related macular degeneration in a primary care population. Invest Ophthalmol Vis Sci. 2015;56:1585–92. DOI: 10.1167/iovs.14-16271
120. Duan Y, Mo J, Klein R, Scott IU, Lin HM, Caulfield J, et al. Age-related macular degeneration is associated with incident myocardial infarction among elderly Americans. Ophthalmology. 2007;114:732–7. DOI: 10.1016/j.ophtha.2006.07.045
121. Wong TY, Tikellis G, Sun C, Klein R, Couper DJ, Sharrett AR. Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology. 2007;114:86–91. DOI: 10.1016/j.ophtha.2006.06.039
122. Sun C, Klein R, Wong TY. Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study. Ophthalmology. 2009;116:1913–9. DOI: 10.1016/j.ophtha.2009.03.046
123. Fernandez AB, Wong TY, Klein R, Collins D, Burke G, Cotch MF, et al. Age-related macular degeneration and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Ophthalmology. 2012;119:765–70. DOI: 10.1016/j.ophtha.2011.09.044
124. Wu J, Uchino M, Sastry SM, Schaumberg DA. Age-related macular degeneration and the incidence of cardiovascular disease: a systematic review and meta-analysis. PLoS One. 2014;9:e89600. DOI: 10.1371/journal.pone.0089600
125. Thomas J, Mohammad S, Charnigo R, Baffi J, Abdel-Latif A, Ziada KM. Age-Related Macular Degeneration and Coronary Artery Disease in a VA Population. South Med J. 2015;108:502–6.
126. Yang K, Wang FH, Liang YB, Wong TY, Wang JJ, Zhan SY, et al. Associations between cardiovascular risk factors and early age-related macular degeneration in a rural Chinese adult population. Retina. 2014;34:1539–53. DOI: 10.1097/IAE.0000000000000118
127. Wang SB, Mitchell P, Chiha J, Liew G, Plant AJ, Thiagalingam A, et al. Severity of coronary artery disease is independently associated with the frequency of early age-related macular degeneration. Br J Ophthalmol. 2015;99:365–70. DOI: 10.1136/bjophthalmol-2014-305793
128. Delcourt C, Michel F, Colvez A, Lacroux A, Delage M, Vernet MH, et al. Associations of cardiovascular disease and its risk factors with age-related macular degeneration: the POLA study. Ophthalmic Epidemiol. 2001;8:237–49. DOI: 10.1076/opep.8.4.237.1613
129. Nguyen-Khoa BA, Goehring EL, Werther W, Gower EW, Do DV, Jones JK. Hospitalized cardiovascular diseases in neovascular age-related macular degeneration. Arch Ophthalmol. 2008;126:1280–6. DOI: 10.1001/archopht.126.9.1280
130. 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;110:25–33. DOI: 10.1016/S0161-6420(02)01565-8
131. van Leeuwen R, Ikram MK, Vingerling JR, Witteman JC, Hofman A, de Jong PT. Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study. Invest Ophthalmol Vis Sci. 2003;44:3771–7. DOI: 10.1167/iovs.03-0121
132. Klein R, Klein BE, Knudtson MD, Cotch MF, Wong TY, Liu K, et al. Subclinical atherosclerotic cardiovascular disease and early age-related macular degeneration in a multiracial cohort: the Multiethnic Study of Atherosclerosis. Arch Ophthalmol. 2007;125:534–43. DOI: 10.1001/archopht.125.4.534
133. Taniguchi H, Shiba T, Maeno T, Takahashi M. Evaluation of Carotid Atherosclerosis, Peripheral Arterial Disease, and Chronic Kidney Disease in Patients with Exudative Age-Related Macular Degeneration without Coronary Artery Disease or Stroke. Ophthalmologica. 2015;233:128–33. DOI: 10.1159/000371716
134. Liao D, Mo J, Duan Y, Klein R, Scott IU, Huang KA, et al. Is age-related macular degeneration associated with stroke among elderly americans? Open Ophthalmol J. 2008;2:37–42. DOI: 10.2174/1874364100802010037
135. Hu CC, Ho JD, Lin HC. Neovascular age-related macular degeneration and the risk of stroke: a 5-year population-based follow-up study. Stroke. 2010;41:613–7. DOI: 10.1161/STROKEAHA.109.571000
136. Tan JS, Wang JJ, Liew G, Rochtchina E, Mitchell P. Age-related macular degeneration and mortality from cardiovascular disease or stroke. Br J Ophthalmol. 2008;92:509–12. DOI: 10.1136/bjo.2007.131706
137. Wieberdink RG, Ho L, Ikram MK, Koudstaal PJ, Hofman A, de Jong PT, et al. Age-related macular degeneration and the risk of stroke: the Rotterdam study. Stroke. 2011;42:2138–42. DOI: 10.1161/STROKEAHA.111.616359
138. Ikram MK, Mitchell P, Klein R, Sharrett AR, Couper DJ, Wong TY. Age-related macular degeneration and long-term risk of stroke subtypes. Stroke. 2012;43:1681–3. DOI: 10.1161/STROKEAHA.112.654632
139. Metelitsina TI, Grunwald JE, DuPont JC, Ying GS. Effect of systemic hypertension on foveolar choroidal blood flow in age related macular degeneration. Br J Ophthalmol. 2006;90:342–6. DOI: 10.1136/bjo.2005.082974
140. Grunwald JE, Hariprasad SM, DuPont J, Maguire MG, Fine SL, Brucker AJ, et al. Foveolar choroidal blood flow in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1998;39:385–90.
141. Grunwald JE, Metelitsina TI, DuPont JC, Ying GS, Maguire MG. Reduced Foveolar Choroidal Blood Flow in Eyes with Increasing AMD Severity. Invest Ophthalmol Vis Sci. 2005;46:1033–8. DOI: 10.1167/iovs.04-1050
142. Vidaurri JS, Pe’er J, Halfon ST, Halperin G, Zauberman H. Association between drusen and some of the risk factors for coronary artery disease. Ophthalmologica. 1984;188:243–7. DOI: 10.1159/000309370
143. Sperduto RD, Hiller R. Systemic hypertension and age-related maculopathy in the Framingham Study. Arch Ophthalmol. 1986;104:216–9. DOI: 10.1001/archopht.1986.01050140070022
144. Hyman L, Schachat AP, He Q, Leske MC. Hypertension, cardiovascular disease, and age-related macular degeneration. Age-Related Macular Degeneration Risk Factors Study Group. Arch Ophthalmol. 2000;118:351–8. DOI: 10.1001/archopht.118.3.351
145. Cougnard-Grégoire A, Delyfer MN, Korobelnik JF, Rougier MB, Malet F, Le Goff M, et al. Long-term blood pressure and age-related macular degeneration: the ALIENOR study. Invest Ophthalmol Vis Sci. 2013;54:1905–12. DOI: 10.1167/iovs.12-10192
146. Yip JL, Khawaja AP, Chan MP, Broadway DC, Peto T, Tufail A, et al. Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study. PLoS One. 2015;10:e0132565. DOI: 10.1371/journal.pone.0132565
147. Cheung CM, Li X, Cheng CY, Zheng Y, Mitchell P, Wang JJ, et al. Prevalence, racial variations, and risk factors of age-related macular degeneration in Singaporean Chinese, Indians, and Malays. Ophthalmology. 2014;121:1598–603. DOI: 10.1016/j.ophtha.2014.02.004
148. Ulaş F, Balbaba M, Özmen S, Çelebi S, Doğan Ü. Association of dehydroepiandrosterone sulfate, serum lipids, C-reactive protein and body mass index with age-related macular degeneration. Int Ophthalmol. 2013;33:485–91. DOI: 10.1007/s10792-013-9728-4
149. Cougnard-Grégoire A, Delyfer MN, Korobelnik JF, Rougier MB, Le Goff M, Dartigues JF, et al. Elevated high-density lipoprotein cholesterol and age-related macular degeneration: the Alienor study. PLoS One. 2014;9:e90973. DOI: 10.1371/journal.pone.0090973
150. Abalain JH, Carre JL, Leglise D, Robinet A, Legall F, Meskar A, et al. Is age-related macular degeneration associated with serum lipoprotein and lipoparticle levels? Clin Chim Acta. 2002;326:97–104. DOI: 10.1016/S0009-8981(02)00288-7
151. Mulero J, Manresa N, Zafrilla P, Losada M. Markers of cardiovascular risk in elderly patients with age-related macular degeneration. Clin Hemorheol Microcirc. 2014;58:447–53.
152. Munch IC, Linneberg A, Larsen M. Precursors of age-related macular degeneration: associations with physical activity, obesity, and serum lipids in the inter99 eye study. Invest Ophthalmol Vis Sci. 2013;54:3932–40. DOI: 10.1167/iovs.12-10785
153. DeAngelis MM, Lane AM, Shah CP, Ott J, Dryja TP, Miller JW. Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration. Arch Ophthalmol. 2004;122:575–80. DOI: 10.1001/archopht.122.4.575
154. Jarrett SG, Boulton ME. Consequences of oxidative stress in age-related macular degeneration. Mol Aspects Med. 2012;33:399–417. DOI: 10.1016/j.mam.2012.03.009
155. Beatty S, Koh HH, Phil M, Henson D, Boulton M. The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration. Surv Ophthalmol. 2000;45:115–34. DOI: 10.1016/S0039-6257(00)00140-5
156. Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol. 2015;71:40–56. DOI: 10.1016/j.vph.2015.03.005
157. He F, Zuo L. Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases. Int J Mol Sci. 2015;16:27770–80. DOI: 10.3390/ijms161126059
158. Handelman GJ, Dratz EA, Reay CC, van Kuijk JG. Carotenoids in the human macula and whole retina. Invest Ophthalmol Vis Sci. 1988;29:850–5.
159. Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris 3rd FL, Gensler G, et al. 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. 2007;125:1225–32. DOI: 10.1001/archopht.125.9.1225
160. SanGiovanni JP, Chew EY, Agrón E, Clemons TE, Ferris 3rd FL, 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;126:1274–9. DOI: 10.1001/archopht.126.9.1274
161. Wu J, Cho E, Willett WC, Sastry SM, Schaumberg DA. Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up. JAMA Ophthalmol. 2015;133(12):1415–24. DOI: 10.1001/jamaophthalmol.2015.3590
162. Writing Group for the AREDS2 Research Group, Bonds DE, Harrington M, Worrall BB, Bertoni AG, Eaton CB, et al. Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med. 2014;174:763–71. DOI: 10.1001/jamainternmed.2014.328
163. Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, Clemons TE, Sangiovanni JP, Danis RP, Ferris 3rd FL, et al. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014;132:142–9. DOI: 10.1001/jamaophthalmol.2013.7376
164. Hall NF, Gale CR, Syddall H, Phillips DI, Martyn CN. Risk of macular degeneration in users of statins: cross sectional study. MJ. 2001;323:375–6. DOI: 10.1136/bmj.323.7309.375
165. McCarty CA, Mukesh BN, Guymer RH, Baird PN, Taylor HR. Cholesterol-lowering medications reduce the risk of age-related maculopathy progression. Med J Aust. 2001;175:340.
166. Wilson HL, Schwartz DM, Bhatt HR, McCulloch CE, Duncan JL. Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration. Am J Ophthalmol. 2004;137:615–24.
167. McGwin G, Xie A, Owsley C. The use of cholesterol-lowering medications and age-related macular degeneration. Ophthalmology. 2005;112:488–94. DOI: 10.1016/j.ophtha.2004.10.027
168. Guymer RH, Chiu AW, Lim L, Baird PN. HMG CoA reductase inhibitors (statins): do they have a role in age-related macular degeneration? Surv Ophthalmol. 2005;50:194–206. DOI: 10.1016/j.survophthal.2004.12.002
169. McGwin G, Modjarrad K, Hall TA, Xie A, Owsley C. 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors and the presence of age-related macular degeneration in the Cardiovascular Health Study. Arch Ophthalmol. 2006;124:33–7. DOI: 10.1001/archopht.124.1.33
170. Maguire MG, Ying G, McCannel CA, Liu C, Dai Y, Complications of Age-related Macular Degeneration Prevention Trial (CAPT) Research Group. Statin use and the incidence of advanced age-related macular degeneration in the Complications of Age-related Macular Degeneration Prevention Trial. Ophthalmology. 2009;116:2381–5. DOI: 10.1016/j.ophtha.2009.06.055
171. Shalev V, Sror M, Goldshtein I, Kokia E, Chodick G. Statin use and the risk of age related macular degeneration in a large health organization in Israel. Ophthalmic Epidemiol. 2011;18:83–90. DOI: 10.3109/09286586.2011.560746
172. Al-Holou SN, Tucker WR, Agrón E, Clemons TE, Cukras C, Ferris 3rd FL, et al. The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9. Ophthalmology. 2015;122(12):2490–6. DOI: 10.1016/j.ophtha.2015.08.028
173. Klein R, Klein BK, Tomany SC, Danforth LG, Cruickshanks KJ. RElation of statin use to the 5-year incidence and progression of age-related maculopathy. Arch Ophthalmol. 2003;121:1151–5. DOI: 10.1001/archopht.121.8.1151
174. Ma L, Wang Y, Du J, Wang M, Zhang R, Fu Y. The association between statin use and risk of age-related macular degeneration. Sci Rep. 2015;5:18280. DOI: 10.1038/srep18280
175. Guymer RH, Dimitrov PN, Varsamidis M, Lim LL, Baird PN, Vingrys AJ, et al. Can HMG Co-A reductase inhibitors (“statins”) slow the progression of age-related macular degeneration? The age-related maculopathy statin study (ARMSS). Clin Interv Aging. 2008;3:581–93. DOI: 10.2147/CIA.S2748
176. Guymer RH, Baird PN, Varsamidis M, Busija L, Dimitrov PN, Aung KZ, et al. Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration. PLoS One. 2013;8:e83759. DOI: 10.1371/journal.pone.0083759
177. Sasaki M, Gan WL, Kawasaki R, Hodgson L, Lee KY, Wong TY, et al. Effect of simvastatin on retinal vascular caliber: the Age-Related Maculopathy Statin Study. Acta Ophthalmol. 2013;91:e418–9. DOI: 10.1111/aos.12114
178. Gehlbach P, Li T, Hatef E. Statins for age-related macular degeneration. Cochrane Database Syst Rev. 2016;8:CD006927.
179. Martini E, Scorolli L, Burgagni M, Fessehaie S. Evaluation of the retinal effects of simvastatin in patients with age-related macular degeneration. Ann Ottalmol Clin Ocul. 1991;117:1121–6.
180. Vavvas DG, Daniels AB, Kapsala ZG, Goldfarb JW, Ganotakis E, Loewenstein JI, et al. Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment. EBioMedicine. 2016;5:198–203. DOI: 10.1016/j.ebiom.2016.01.033
181. Age-Related Macular Degeneration (AMD) | National Eye Institute [https://nei.nih.gov/eyedata/amd#4]. Accessed 23 Nov 2015.
182. Snow KK, Cote J, Yang W, Davis NJ, Seddon JM. Association between reproductive and hormonal factors and age-related maculopathy in postmenopausal women. Am J Ophthalmol. 2002;134:842–8. DOI: 10.1016/S0002-9394(02)01755-5
183. Laitinen A, Laatikainen L, Härkänen T, Koskinen S, Reunanen A, Aromaa A. Prevalence of major eye diseases and causes of visual impairment in the adult Finnish population: a nationwide population-based survey. Acta Ophthalmol. 2010;88:463–71. DOI: 10.1111/j.1755-3768.2009.01566.x
184. Buch H, Nielsen NV, Vinding T, Jensen GB, Prause JU, la Cour M. 14-year incidence, progression, and visual morbidity of age-related maculopathy: the Copenhagen City Eye Study. Ophthalmology. 2005;112:787–98. DOI: 10.1016/j.ophtha.2004.11.040
185. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case–control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. Ophthalmology. 2000;107:2224–32. DOI: 10.1016/S0161-6420(00)00409-7
186. Roh MI, Kim JH, Byeon SH, Koh HJ, Lee SC, Kwon OW. Estimated prevalence and risk factor for age-related maculopathy. Yonsei Med J. 2008;49:931–41. DOI: 10.3349/ymj.2008.49.6.931
187. You QS, Xu L, Yang H, Li YB, Wang S, Wang JD, et al. Five-year incidence of age-related macular degeneration: the Beijing Eye Study. Ophthalmology. 2012;119:2519–25. DOI: 10.1016/j.ophtha.2012.06.043
188. Fong DS, Contreras R. Recent statin use and 1-year incidence of exudative age-related macular degeneration. Am J Ophthalmol. 2010;149:955–8. e1. DOI: 10.1016/j.ajo.2009.12.037
189. Hirvelä H, Luukinen H, Läärä E, Sc L, Laatikainen L. Risk factors of age-related maculopathy in a population 70 years of age or older. Ophthalmology. 1996;103:871–7. DOI: 10.1016/S0161-6420(96)30593-9
190. Chakravarthy U, Wong TY, Fletcher A, Piault E, Evans C, Zlateva G, et al. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol. 2010;10:31. DOI: 10.1186/1471-2415-10-31
191. Smith W, Mitchell P, Wang JJ. Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Aust N Z J Ophthalmol. 1997;25 Suppl 1:S13–5. DOI: 10.1111/j.1442-9071.1997.tb01745.x
192. Rudnicka AR, Jarrar Z, Wormald R, Cook DG, Fletcher A, Owen CG. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis. Ophthalmology. 2012;119:571–80. DOI: 10.1016/j.ophtha.2011.09.027
193. Zetterberg M. Age-related eye disease and gender. Maturitas. 2016;83:19–26. DOI: 10.1016/j.maturitas.2015.10.005
194. van Leeuwen R, Tomany SC, Wang JJ, Klein R, Mitchell P, Hofman A, et al. Is medication use associated with the incidence of early age-related maculopathy? Pooled findings from 3 continents. Ophthalmology. 2004;111:1169–75. DOI: 10.1016/j.ophtha.2003.10.024
195. Naderi S, Cho LS. Cardiovascular disease in women: prevention, symptoms, diagnosis, pathogenesis. Cleve Clin J Med. 2013;80:577–87. DOI: 10.3949/ccjm.80a.13005
196. Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001;135:939–53. DOI: 10.7326/0003-4819-135-11-200112040-00005
197. Hodis HN, Collins P, Mack WJ, Schierbeck LL. The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective. Climacteric. 2012;15:217–28. DOI: 10.3109/13697137.2012.656401
198. Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health (Larchmt). 2006;15:35–44. DOI: 10.1089/jwh.2006.15.35
199. Herrington DM, Vittinghoff E, Lin F, Fong J, Harris F, Hunninghake D, et al. Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS). Circulation. 2002;105:2962–7. DOI: 10.1161/01.CIR.0000019406.74017.B2
200. Berglind IA, Andersen M, Citarella A, Linder M, Sundström A, Kieler H. Hormone therapy and risk of cardiovascular outcomes and mortality in women treated with statins. Menopause. 2015;22:369–76. DOI: 10.1097/GME.0000000000000345
201. Dehghan A, Bis JC, White CC, Smith AV, Morrison AC, Cupples LA, et al. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium. PLoS One. 2016;11:e0144997. DOI: 10.1371/journal.pone.0144997
202. Feehan M, Hartman J, Durante R, Morrison MA, Miller JW, Kim IK, et al. Identifying subtypes of patients with neovascular age-related macular degeneration by genotypic and cardiovascular risk characteristics. BMC Med Genet. 2011;12:83. DOI: 10.1186/1471-2350-12-83
203. Curcio CA, Johnson M, Rudolf M, Huang JD. The oil spill in ageing Bruch membrane. Br J Ophthalmol. 2011;95:1638–45. DOI: 10.1136/bjophthalmol-2011-300344
204. Vaya J. The association between biomarkers in the blood and carotid plaque composition-focusing on oxidized lipids, oxysterols and plaque status. Biochem Pharmacol. 2013;86:15–8. DOI: 10.1016/j.bcp.2013.01.025
205. Machalinska A, Safranow K, Dziedziejko V, Mozolewska-Piotrowska K, Paczkowska E, Klos P, et al. Different populations of circulating endothelial cells in patients with age-related macular degeneration: a novel insight into pathogenesis. Invest Ophthalmol Vis Sci. 2011;52:93–100. DOI: 10.1167/iovs.10-5756
206. Castellon X, Bogdanova V. Chronic Inflammatory Diseases and Endothelial Dysfunction. Aging Dis. 2016;7:81–9. DOI: 10.14336/AD.2015.0803
207. McHarg S, Clark SJ, Day AJ, Bishop PN. Age-related macular degeneration and the role of the complement system. Mol Immunol. 2015;67:43–50. DOI: 10.1016/j.molimm.2015.02.032
208. Vlaicu SI, Tatomir A, Rus V, Mekala AP, Mircea PA, Niculescu F, et al. The role of complement activation in atherogenesis: the first 40 years. Immunol Res. 2016;64:1–13. DOI: 10.1007/s12026-015-8669-6
209. Fanjul-Moles ML, López-Riquelme GO. Relationship between Oxidative Stress, Circadian Rhythms, and AMD. Oxid Med Cell Longev. 2016;2016:7420637. DOI: 10.1155/2016/7420637
210. Lambert V, Munaut C, Jost M, Noël A, Werb Z, Foidart JM, et al. Matrix metalloproteinase-9 contributes to choroidal neovascularization. Am J Pathol. 2002;161:1247–53. DOI: 10.1016/S0002-9440(10)64401-X
211. Galis ZS, Khatri JJ. Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis The Good, the Bad, and the Ugly. Circ Res. 2002;90:251–62.
212. Vine AK, Stader J, Branham K, Musch DC, Swaroop A. Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. Ophthalmology. 2005;112:2076–80. DOI: 10.1016/j.ophtha.2005.07.004
213. Grunin M, Hagbi-Levi S, Chowers I. The role of monocytes and macrophages in age-related macular degeneration. Adv Exp Med Biol. 2014;801:199–205. DOI: 10.1007/978-1-4614-3209-8_26
214. Chistiakov DA, Bobryshev YV, Nikiforov NG, Elizova NV, Sobenin IA, Orekhov AN. Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes. Int J Cardiol. 2015;184:436–45. DOI: 10.1016/j.ijcard.2015.03.055
215. Chistiakov DA, Orekhov AN, Bobryshev YV. Vascular smooth muscle cell in atherosclerosis. Acta Physiol (Oxf). 2015;214:33–50. DOI: 10.1111/apha.12466
216. Berenberg TL, Metelitsina TI, Madow B, Dai Y, Ying GS, Dupont JC, et al. The association between drusen extent and foveolar choroidal blood flow in age-related macular degeneration. Retina. 2012;32:25–31. DOI: 10.1097/IAE.0b013e3182150483
217. Lowe GD. Virchow’s triad revisited: abnormal flow. Pathophysiol Haemost Thromb. 2003;33:455–7. DOI: 10.1159/000083845
218. Bhutto I, Lutty G. Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex. Mol Aspects Med. 2012;33:295–317. DOI: 10.1016/j.mam.2012.04.005
219. Moreno PR, Purushothaman M, Purushothaman KR. Plaque neovascularization: defense mechanisms, betrayal, or a war in progress. Ann N Y Acad Sci. 2012;1254:7–17. DOI: 10.1111/j.1749-6632.2012.06497.x
220. Badimon L, Vilahur G. Thrombosis formation on atherosclerotic lesions and plaque rupture. J Intern Med. 2014;276:618–32. DOI: 10.1111/joim.12296
221. Toy BC, Krishnadev N, Indaram M, Cunningham D, Cukras CA, Chew EY, et al. Drusen regression is associated with local changes in fundus autofluorescence in intermediate age-related macular degeneration. Am J Ophthalmol. 2013;156:532–42. e1. DOI: 10.1016/j.ajo.2013.04.031
222. Ohno-Matsui K. Parallel findings in age-related macular degeneration and Alzheimer’s disease. Prog Retin Eye Res. 2011;30:217–38. DOI: 10.1016/j.preteyeres.2011.02.004
223. Jans DM, Martinet W, Van De Parre TJ, Herman AG, Bult H, Kockx MM, et al. Processing of amyloid precursor protein as a biochemical link between atherosclerosis and Alzheimer’s disease. Cardiovasc Hematol Disord Drug Targets. 2006;6:21–34. DOI: 10.2174/187152906776092695
224. Linton MF, Yancey PG, Davies SS, Jerome WGJ, Linton EF, Vickers KC. The Role of Lipids and Lipoproteins in Atherosclerosis. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth: MDText.com, Inc; 2000.
225. McNeish J, Aiello RJ, Guyot D, Turi T, Gabel C, Aldinger C, et al. High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1. Proc Natl Acad Sci U S A. 2000;97:4245–50. DOI: 10.1073/pnas.97.8.4245