Using current data to define new approach in age related macular degeneration: Need to accelerate translational research

Current Genomics

Volumn 15, Issue 4, 2014, Pages 266-277

  Anand, Akshay ^a   Sharma, Kaushal ^a   Chen, Wei ^b   Sharma, Neel Kamal ^c  

^a POSTGRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCH   (India)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c NATIONAL EYE INSTITUTE   (United States)

Author keywords

Age related macular degeneration; Bio informatics; Biomarkers; Epigenetics; Mitochondrial genes; SNP; Translational research

Indexed keywords

EID: 84905637871     PISSN: 13892029     EISSN: 18755488     Source Type: Journal    
DOI: 10.2174/1389202915666140516204512     Document Type: Review

References (90)

1. Chakravarthy, U.; Wong, T.Y.; Fletcher, A.; Piault, E.; Evans, C.; Zlateva, G.; Buggage, R.; Pleil, A.; Mitchell, P. Clinical risk factors for age related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol., 2010, 10, 31.
2. Chong, E.W.; Robman, L.D.; Simpson, J.A.; Hodge, A.M.; Aung, K.Z.; Dolphin, T.K.; English, D.R.; Giles, G.G.; Guymer, R.H. Fat consumption and its association with age-related macular degeneration. Arch. Ophthalmol., 2009, 127, 674-680.
3. Seddon, J.M.; George, S.; Rosner, B. Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with agerelated macular degeneration: the US Twin Study of Age-related Macular Degeneration. Arch. Ophthalmol., 2006, 124, 995-1001.
4. Delcourt, C.; Carrière, I.; Delage, M.; Barberger-Gateau, P.; Schalch, W. POLA Study Group. Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for agerelated maculopathy and cataract: the POLA Study. Invest. Ophthalmol. Vis. Sci., 2006, 47, 2329-2335.
5. Age-Related Eye Disease Study Research Group; San Giovanni, J.P.; Chew, E.Y.; Clemons, T.E.; Ferris, F.L.; Gensler, G.; Lindblad, A.S.; Milton, R.C.; Seddon, J.M.; Sperduto, R.D. 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, 1225-1232.
6. Munoz, B.; Klein, R.; Rodriguez, J.; Snyder, R.; West, S.K. Prevalence of age-related macular degeneration in a population-based sample of Hispanic people in Arizona: Proyecto VER. Arch. Ophthalmol., 2005, 123(11), 1575-1580.
7. Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan, I.; Kelly, S.P. Smoking and age related macular degeneration: A review of association. Eye (Lond), 2005, 19(9), 935-944.
8. Klein, R. Overview of progress in the epidemiology of age-related macular degeneration. Ophthalmic Epidemiol., 2007, 14(4), 184-187.
9. Melrose, M.A.; Magargal, L.E.; Lucier, A.C. Identical twins with subretinal neovascularization complicating senile macular degeneration. Ophthalmic Surg., 1985, 16, 648-51.
10. Meyers, S.M.; Zachary, A.A. Monozygotic twins with age-related macular degeneration. Arch. Ophthalmol., 1988, 106, 651-3.
11. Dosso, A.A.; Bovet, J. Monozygotic twin brothers with age-related macular degeneration. Ophthalmologica, 1992, 205, 24-8.
12. Piguet, B.; Wells, J.A.; Palmvang, I.B.; Wormald, R.; Chisholm, I.H.; Bird, A.C. Age related Bruch's membrane change: a clinical study of the relative role of heredity and environment. Br. J. Ophthalmol., 1993, 77, 400-3.
13. Klein, M.L.; Mauldin, W.M.; Stoumbos, V.D. Heredity and agerelated macular degeneration: observations in monozygotic twins. Arch. Ophthalmol., 1994, 112, 932-7.
14. Seddon, J.M.; Ajani, U.A.; Mitchell, B.D. Familial aggregation of age-related maculopathy. Am. J. Ophthalmol., 1997, 123, 199-206.
15. Sharma, N.K.; Gupta, A.; Prabhakar, S.; Singh, R.; Sharma, S.K.; Chen, W.; Anand, A. Association between CFH Y402H polymorphism and age related macular degeneration in North Indian cohort. PLoS One, 2013, 8(7), e70193.
16. Klaver, C.C.; Wolfs, R.C.; Assink, J.J.; van Duijn, C.M.; Hofman, A.; de Jong, P.T. Genetic risk of age-related maculopathy: population-based familial aggregation study. Arch. Ophthalmol., 1998, 116, 1646-51.
17. Assink, J.J.; Klaver, C.C.; Houwing-Duistermaat, J.J.; Wolfs, R.C.; van Duijn, C.M.; Hofman, A.; de Jong, P.T. Heterogeneity of the genetic risk in age-related macular disease: a population-based familial risk study. Ophthalmology, 2005, 112, 482-7.
18. Zareparsi, S.; Branham, K.E.; Li, M.; Shah S, Klein R.J.; Hoh, J.; Abecasis, G.R.; Swaroop, A. Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration. Am. J. Hum. Genet., 2005, 77, 149-153.
19. Sepp, T.; Khan, J.C.; Thurlby, D.A.; Shahid, H.; Clayton, D.G.; Moore, A.T.; Bird, A.C.; Yates, J.R. Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers. Invest. Ophthalmol. Vis. Sci., 2006, 47, 536-540.
20. Hageman, G.S.; Anderson, D.H.; Johnson, L.V.; Hancox, L.S.; Taiber, A.J.; Hardisty, L.I.; Hageman, J.L.; Stockman, H.A.; Borchardt, J.D.; Gehrs, K.M.; Smith, R.J.; Silvestri, G.; Russell, S.R.; Klaver, C.C.; Barbazetto, I.; Chang, S.; Yannuzzi, L.A.; Barile, G.R.; Merriam, J.C.; Smith, R.T.; Olsh, A.K.; Bergeron, J.; Zernant, J.; Merriam, J.E.; Gold, B.; Dean, M.; Allikmets, R. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. USA, 2005, 102, 7227-32.
21. Gehrs, K.M.; Jackson, J.R.; Brown, E.N.; Allikmets, R.; Hageman, G.S. Complement, age-related macular degeneration and a vision of the future. Arch. Ophthalmol., 2010, 128, 349-58.
22. Boon, C.J.; Klevering, B.J.; Hoyng, C.B.; Zonneveld-Vrieling, M.N.; Nabuurs, S.B.; Blokland, E.; Cremers, F.P.; den Hollander, A.I. Basal laminar drusen caused by compound heterozygous variants in the CFH gene. Am. J. Hum. Genet., 2008, 82, 516-23.
23. de Jong, P.T. Age-related macular degeneration. N. Engl. J. Med., 2006, 355(14),1474-85.
24. Mullins, R.F.; Skeie, J.M.; Folk, J.C.; Solivan-Timpe, F.M.; Oetting, T.A.; Huang, J.; Wang, K.; Stone, E.M.; Fingert, J.H. Evaluation of variants in the selectin genes in age related macular degeneration. BMC Med. Genet., 2011, 12, 58.
25. Yang, Z.; Stratton, C.; Francis, P.J.; Kleinman, M.E.; Tan, P.L.; Gibbs, D.; Tong, Z.; Chen, H.; Constantine, R.; Yang, X.; Chen, Y.; Zeng, J.; Davey, L.; Ma, X.; Hau, V.S.; Wang, C.; Harmon, J.; Buehler, J.; Pearson, E.; Patel, S.; Kaminoh, Y.; Watkins, S.; Luo, L.; Zabriskie, N.A.; Bernstein, P.S.; Cho, W.; Schwager, A.; Hinton, D.R.; Klein, M.L.; Hamon, S.C.; Simmons, E.; Yu, B.; Campochiaro, B.; Sunness, J.S.; Campochiaro, P.; Jorde, L.; Parmigiani, G.; Zack, D.J.; Katsanis, N.; Ambati, J.; Zhang, K. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N. Engl. J. Med., 2008, 359, 1456-1463.
26. Kaneko, H.; Dridi, S.; Tarallo, V.; Gelfand, B.D.; Fowler, B.J.; Cho, W.G.; Kleinman, M.E.; Ponicsan, S.L.; Hauswirth, W.W.; Chiodo, V.A.; Karikó, K.; Yoo, J.W.; Lee, D.K.; Hadziahmetovic, M.; Song, Y.; Misra, S.; Chaudhuri, G.; Buaas, F.W.; Braun, R.E.; Hinton, D.R.; Zhang, Q.; Grossniklaus, H.E.; Provis, J.M.; Madigan, M.C.; Milam, A.H.; Justice, N.L.; Albuquerque, R.J.; Blandford, A.D.; Bogdanovich, S.; Hirano, Y.; Witta, J.; Fuchs, E.; Littman, D.R.; Ambati, B.K.; Rudin, C.M.; Chong, M.M.; Provost, P.; Kugel, J.F.; Goodrich, J.A.; Dunaief, J.L.; Baffi, J.Z.; Ambati, J. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature, 2011, 471(7338), 325-30.
27. Sharma, N.K.; Gupta, A.; Prabhakar, S.; Singh, R.; Sharma, S.; Anand, A. Single Nucleotide Polymorphism and Serum Levels of VEGFR2 are Associated with Age Related Macular Degeneration. Curr. Neurovasc. Res., 2012, 9, 256-265.
28. Almeida, L.N.; Melilo-Carolino, R.; Veloso, C.E.; Pereira, P.A.; Miranda, D.M.; De Marco, L.A.; Nehemy, M.B. Homozygosity for the +674C>T polymorphism on VEGF gene is associated with age-related macular degeneration in a Brazilian cohort. Graefes Arch. Clin. Exp. Ophthalmol., 2012, 250(2), 185-189.
29. Sharma, N.K.; Gupta, A.; Prabhakar, S.; Singh, R.; Bhatt, A.K.; Anand, A. CC chemokine receptor-3 as new target for age-related macular degeneration. Gene, 2013, 523, 106-111.
30. Thakkinstian, A.; McEvoy, M.; Chakravarthy, U.; Chakrabarti, S.; McKay, G.J.; Ryu, E.; Silvestri, G.; Kaur, I.; Francis, P.; Iwata, T.; Akahori, M.; Arning, A.; Edwards, A.O.; Seddon, J.M.; Attia, J. The Association between Complement Component 2/Complement Factor B Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis. Am. J. Epidemiol., 2012, 176(5), 361-372.
31. Mantel, I.; Ambresin, A.; Moetteli, L.; Droz, I; Roduit, R.; Munier, F.L.; Schorderet, D.F. Complement Factor B Polymorphism and the Phenotype of Early Age-related Macular Degeneration. Ophthalmic Genet., 2014, 35(1), 12-17.
32. Sundaresan, P.; Vashist, P.; Ravindran, R.D.; Shanker, A.; Nitsch, D.; Nonyane, B.A.; Smeeth, L.; Chakravarthy, U.; Fletcher, A.E. Polymorphisms in ARMS2/HTRA1 and complement genes and age-related macular degeneration in India: findings from the INDEYE study. Invest. Ophthalmol. Vis. Sci., 2012, 53(12), 7492-7.
33. Sharma, N.K.; Prabhakar, S.; Gupta, A.; Singh, R.; Gupta, P.K.; Gupta, P.K.; Anand, A. New biomarker for neovascular agerelated macular degeneration: eotaxin-2. DNA Cell Biol., 2012, 31(11),1618-27.
34. Anand, A.; Sharma, N.K.; Singh, R.; Gupta, A.; Prabhakar, S.; Jindal, N.; Bhatt, A.K.; Sharma, S.K.; Gupta, P.K. Does DcR1 (TNF-related apoptosis-inducing-ligand Receptor 3) have any role in human AMD pathogenesis? Sci. Rep., 2014, 4, 4114.
35. Anand, A.; Sharma, N.K.; Gupta, A.; Prabhakar, S.; Sharma, S.K.; Singh, R.; Gupta, P.K. Single nucleotide polymorphisms in MCP-1 and its receptor are associated with the risk of age related macular degeneration. PLoS One, 2012, 7(11), e49905.
36. Holliday, E.G.; Smith, A.V.; Cornes, B.K.; Buitendijk, GH.; Jensen, R.A.; Sim, X.; Aspelund, T.; Aung, T.; Baird, P.N.; Boerwinkle, E.; Cheng, C.Y.; van Duijn, C.M.; Eiriksdottir, G.; Gudnason, V.; Harris, T.; Hewitt, A.W.; Inouye, M.; Jonasson, F.; Klein, B.E.; Launer, L, Li, X.; Liew, G.; Lumley, T.; McElduff, P.; McKnight, B.; Mitchell, P.; Psaty, B.M.; Rochtchina, E.; Rotter, J.I.; Scott, R.; Tay, W.; Taylor, K.; Teo, Y.Y.; Uitterlinden, A.G.; Viswanathan, A.; Xie, S.; Wang, J.J. Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis. PLoS One, 2013, 8(1), e53830.
37. Chen, W.; Stambolian, D.; Edwards, A.O.; Branham, K.E.; Othman, M.; Jakobsdottir, J.; Tosakulwong, N.; Pericak-Vance, M.A.; Campochiaro, P.A.; Klein, M.L.; Tan, P.L.; Conley, Y.P.; Kanda, A.; Kopplin, L.; Li, Y.; Zack, D.J.; Chew, E.Y.; Heckenlively, J.R.; Yoshimura, N.; Iyengar, S.K.; Francis, P.J.; Katsanis, N.; Seddon, J.M.; Haines, J.L.; Gorin, M.B.; Abecasis, G.R.; Swaroop, A. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc. Natl. Acad. Sci. USA, 2010, 107(16), 7401-6.
38. Tian, J.; Yu, W.; Qin, X. Association of genetic polymorphisms and age-related macular degeneration in Chinese population. Invest. Ophthalmol. Vis. Sci., 2012, 53, 4262-4269.
39. Jarrett, S.G.; Lin, H.; Godley, B.F.; Boulton, M.E. Mitochondrial DNA damage and its potential role in retinal degeneration. Prog. Retin. Eye Res. 2008, 27, 596-607.
40. Gredilla, R.; Bohr, V.A.; Stevnsner, T. Mitochondrial DNA repair and association with aging-an update. Exp. Gerontol., 2010, 45, 478-488.
41. Barron, M.J.; Johnson, M.A.; Andrews, R.M.; Clarke, M.P.; Griffiths, P.G.; Bristow, E.; He, L.P.; Durham, S.; Turnbull, D.M. Mitochondrial abnormalities in ageing macular photoreceptors. Invest. Ophthalmol. Vis. Sci., 2001, 42, 3016-3022.
42. Kenney, M.C.; Atilano, S.R.; Boyer, D.; Chwa, M.; Chak, G.; Chinichian, S.; Coskun, P.; Wallace, D.C.; Nesburn, A.B.; Udar, N.S. Characterization of retinal and blood mitochondrial DNA from age-related macular degeneration patients. Invest. Ophthalmol. Vis. Sci., 2010, 51, 4289-4297.
43. Jones, M.M.; Manwaring, N.; Wang, J.J.; Rochtchina, E.; Mitchell, P.; Sue, C.M. Mitochondrial DNA haplogroups and age-related maculopathy. Arch. Ophthalmol., 2007, 125, 1235-1240.
44. Canter, J.A.; Olson, L.M.; Spencer, K.; Schnetz-Boutaud, N. Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration. PLoS One, 2008, 3, e2091.
45. San Giovanni, J.P.; Arking, D.E.; Iyengar, S.K. Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration. PLoS One, 2009, 4, e5508.
46. Bollati, V.; Schwartz, J.; Wright, R. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech. Ageing Dev., 2009, 130, 234-239.
47. Eckmiller, M.S. Defective cone photoreceptor cytoskeleton, alignment, feedback, and energetics can lead to energy depletion in macular degeneration. Prog. Retin. Eye Res., 2004, 23(5), 495-522.
48. Marchenko, G.N.; Strongin, A.Y. MMP-28, a new human matrixmetalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors. Gene, 2001, 265(1-2), 87-93.
49. Primakoff, P.; Myles, D.G. The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet., 2000, 16(2), 83-87.
50. Wight, T.N. The ADAMTS Proteases, Extracellular Matrix, and Vascular Disease. Arterioscler. Thromb. Vasc. Biol., 2005, 25, 12-14.
51. Du, W.; Wang, S.; Zhou, Q. ADAM TS9 is a functional tumor suppressor through inhibiting AKT/mTOR pathway and associated with poor survival in gastric cancer. Oncogene, 2013, 32, 3319-3328.
52. Jomary, C.; Cullen, J.; Jones, S.E. Inactivation of the Akt Survival Pathway during Photoreceptor Apoptosis in the Retinal Degeneration Mouse. IOVS, 2006, 47, 41620-1629.
53. Zhao, C.; Yasumura, D.; Li, X. mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice. J. Clin. Invest., 2011, 121(1), 369-383.
54. Bornstein, P. Thrombospondins function as regulators of angiogenesis. JCCS, 2009, 3(3-4), 189-200.
55. Dickersin, K.; Min, Y.I.; Meinert, C.L. Factors influencing publication of research results. Follow-up of applications submitted to two institutional review boards. JAMA, 1992, 267, 374-8.
56. Easterbrook, P.J.; Berlin, J.A.; Gopalan, R.; Matthews, D.R. Publication bias in clinical research. Lancet, 1991, 337, 867-72.
57. Begg, C.B.; Berlin, J.A. Publication bias: a problem in interpreting medical data. J. R. Stat. SOC A., 1988, 151, 419-63.
58. Naj, A.C.; Scott, W.K.; Courtenay, M.D.; Cade, W.H. Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis. Ann. Hum. Genet., 2013, 77(3), 215-31.
59. Seddon, J.M.; Yu, Y.; Miller, E.C.; Reynolds, R.; Tan, P.L.; Gowrisankar, S.; Goldstein, J.I.; Triebwasser, M.; Anderson, H.E.; Zerbib, J.; Kavanagh, D.; Souied, E.; Katsanis, N.; Daly, M.J.; Atkinson, J.P.; Raychaudhuri, S. Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat. Genet., 2013, 45(11), 1366-70.
60. Fritsche, L.G.; Chen, W.; Schu, M.; Yaspan, B.L.; Yu, Y.; Thorleifsson, G.; Zack, D.J.; Arakawa, S.; Cipriani, V.; Ripke, S.; Igo, R.P.; Buitendijk G.H.; Sim X, Weeks, D.; Guymer, R.H.; Merriam, J.E.; Francis, P.J.; Hannum, G.; Farrer, L.A.; Heid, I.M.; Abecasis, R. Seven new loci associated with age-related macular degeneration. Nat. Genet., 2013, 45(4), 433-9.
61. Holliday, E.G.; Smith, A.V.; Cornes, B.K. Insights intothe genetic architecture of early stage agerelated macular degeneration: a genome wide association study meta-analysis. PLoS One, 2013, 8(1), e53830.
62. Sobrin, L.; Ripke, S.; Yu, Y. Heritability and genomewide association study to assess genetic differences between advanced age related macular degeneration subtypes. Ophthalmology, 2012, 119(9), 1874-85.
63. Cipriani, V.; Leung, H.; Plagnol, V.; Bunce C. Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3. Hum. Mol. Genet., 2012, 21(18), 4138-50.
64. Arakawa, S.; Takahashi, A.; Ashikawa, K. Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population. Nat. Genet., 2011, 43, 1001-1004.
65. Yu, Y.; Bhangale, T.R.; Fagerness, J. Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. Hum. Mol. Genet., 2011, 20(18), 3699-09.
66. Ryu, E.; Fridley, B.L.; Tosakulwong, N.; Bailey, K.R.; Edwards, A.O. Genome-wide association analyses of genetic, phenotypic, and environmental risks in the age-related eye disease study. Mol. Vis., 2010, 16, 2811-21.
67. Zerhouni, E. The NIH roadmap. Science, 2003, 72(302), 63-64.
68. AAMC: Task Force II on Clinical Research. Promoting translational and clinical science: the critical role of medical schools and teaching hospitals. Washington, DC. Association of American Medical Colleges, 2006.
69. Murillo, H.; Reece, E.A.; Snyderman, R.; Sung, N.S. Meeting the challenges facing clinical research: solutions proposed by leaders of medical specialty and clinical research societies. Acad. Med., 2006, 81(2), 107-112.
70. Institute of Medicine: Crossing the Quality Chasm a New Health System for the 21st Century. Washington DC: National Academy Press, 2001.
71. Tunis, S.R.; Stryer, D.B.; Clancy, C.M. Pratical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA, 2003, 290, 1624-1632.
72. Macpherson, H. Pragmatic clinical trials. Complement Ther. Med., 2004, 12(2-3), 136-140.
73. Thomas, D.C.; Conti, D.V. Commentary: the concept of 'Mendelian Randomization. Int. J. Epidemiol., 2004, 33, 21-25
74. Gaudreault, J.; Fei, D.; Rusit, J.; Suboc, P.; Shiu, V. Preclinical Pharmacokinetics of Ranibizumab (rhuFabV2) after a Single Intravitreal Administration. Invest. Ophthalmol. Vis. Sci., 2005, 46(2), 726-733.
75. Gaudreault, J.; Fei, D.; Beyer, J.C. Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody fragment directed against VEGF-A, following intravitreal administration in rabbits. Retina, 2007, 27(9), 1260-6.
76. Thaler, S.; Fiedorowicz, M.; Choragiewicz, T.J. Toxicity testing of the VEGF inhibitors bevacizumab, ranibizumab and pegaptanib in rats both with and without prior retinal ganglion cell damage. Acta Ophthalmol., 2010, 88(5), e170-6.
77. Adamo, J.E.; Bauer, G.; Berro, M. A Roadmap for Academic Health Centers to Establish Good Laboratory Practice-Compliant Infrastructure. Acad. Med., 2012, 87(3), 279-284.
78. Clarke, J.J.; Lawlor, T.E.; Madraymootoo, W.; Pant, K.; Young, R.R.; Wagner, V.O., Aardema, M.J. Summary of in vitro genetic toxicology assay results: expected and unexpected effects of recent study design modifications. Environ. Mol. Mutagen, 2012, 53(8), 631-5.
79. Age-Related Eye Disease Study Research Group. A randomized, placebo controlled, clinical trial of highdose supplementation with vitamins C and E, beta-caroten, and zinc for agerelated macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol., 2001, 119(10), 1417-36.
80. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of highdose supplementation with vitamins C and E and betacarotene for agerelated cataract and vision loss: AREDS report no. 9. Arch. Ophthalmol., 2001, 119(10), 1439-52.
81. Age-Related Eye Disease Study 2 Research Group. Lutein+zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye DiseaseStudy 2 (AREDS2) randomized clinical trial. JAMA, 2013, 309(19), 2005-15.
82. Seddon, J.M.; Reynolds, R.; Maller, J.; Fagerness, J.A.; Daly, M.J.; Rosner, B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest. Ophthalmol. Vis. Sci., 2009, 50(5), 2044-53.
83. Klein, M.L.; Francis, P.J.; Ferris, F.L. 3rd.; Hamon, S.C.; Clemons, T.E. Risk assessment model for development of advanced agerelated macular degeneration. Arch. Ophthalmol., 2011, 129(12), 1543-50.
84. Seddon, J.M.; Reynolds, R.; Yu, Y.; Rosner, B. Validation of a prediction algorithm for progression to advanced macular degeneration subtypes. JAMA Ophthalmol., 2013, 131(4), 448-55.
85. Hu, Y.; Li, L.; Ehm, M.G.; Bing, N.; Song, K.; Nelson, M.The benefits of using genetic information to design prevention trials. Am. J. Hum. Genet., 2013, 92(4), 547-57.
86. Güngör, K.; Hotez, P.J.; Ozdemir, V.; Aynacioglu, S. Glaucomics: A Call for Systems Diagnostics for 21(st) Century Ophthalmology and Personalized Visual Health. OMICS, 2014, 18(5), 275-9.
87. Elrakaiby, M.; Dutilh, B.E.; Rizkallah, M.R.; Boleij, A.; Cole, J.N.; Aziz, R.K. Pharmacomicrobiomics:The Impact of Human Microbiome Variations on Systems Pharmacology and Personalized Therapeutics. OMICS, 2014 [in press].
88. Ozdemir, V.; Endrenyi, L.; Aynacioglu, S. Bernard Lerer: recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics). OMICS, 2014, 18(4), 211-21.
89. Bowler, R.P.; Bahr, T.M.; Hughes, G.; Lutz, S.; Kim, Y.I.; Coldren, C.D.; Reisdorph, N.; Kechris, K.J. Integrative omics approach identifies interleukin-16 as a biomarker of emphysema. OMICS, 2013, 17(12), 619-26.
90. Sabbadini, R.A. Sphingosine-1-phosphate antibodies as potential agents in the treatment of cancer and age-related macular degeneration. Br. J. Pharmacol., 2011, 162(6), 1225-38.