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Abstract

Age-related macular degeneration (AMD) is a chronic degenerative disease of the central retina and a major cause of vision impairment and blindness with millions of people affected in the elderly population. In recent years, considerable efforts have been made to understand disease pathology with the long-term goal of designing novel and effective treatment options for this devastating disease. Although striking advances in treating the neovascular stage of late AMD have occurred, no therapy is available for almost half of all AMD patients, specifically those who are affected by the atrophic form of the disease. This review highlights current knowledge on the genetic factors associated with early- and late-stage forms of the disease. It also summarizes the findings regarding the extent to which these factors may play a role in the transition from one disease stage to another, and it emphasizes the need to explore further the underlying mechanisms for both development and progression of this disease as a starting point for designing innovative therapies for it.

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What Does Genetics Tell Us About Age-Related Macular Degeneration?
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2015-11-24
2024-05-02
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Literature Cited

  1. Ach T, Huisingh C, McGwin G, Messinger JD, Zhang T. et al. 2014. Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 55:84832–41 [Google Scholar]
  2. Adamis AP, Shima DT, Yeo KT, Yeo TK, Brown LF. et al. 1993. Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem. Biophys. Res. Commun. 193:2631–38 [Google Scholar]
  3. Adams WJ, Zhang Y, Cloutier J, Kuchimanchi P, Newton G. et al. 2013. Functional vascular endothelium derived from human induced pluripotent stem cells. Stem Cell Rep. 1:2105–13 [Google Scholar]
  4. Aickin M, Gensler H. 1996. Adjusting for multiple testing when reporting research results: the Bonferroni versus Holm methods. Am. J. Public Health 86:5726–28 [Google Scholar]
  5. Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA. et al. 1997. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 277:53331805–7 [Google Scholar]
  6. Alten F, Eter N. 2015. Current knowledge on reticular pseudodrusen in age-related macular degeneration. Br. J. Ophthalmol. 99:717–22 [Google Scholar]
  7. Anderson DH, Mullins RF, Hageman GS, Johnson L V. 2002. A role for local inflammation in the formation of drusen in the aging eye. Am. J. Ophthalmol. 134:3411–31 [Google Scholar]
  8. Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J. et al. 2014. An atlas of active enhancers across human cell types and tissues. Nature 507:7493455–61 [Google Scholar]
  9. AREDS (Age-Related Eye Dis. Study Res. Group) 2001. 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. 119:101417–36 [Google Scholar]
  10. Baird PN, Richardson AJ, Robman LD, Dimitrov PN, Tikellis G. et al. 2006. Apolipoprotein (APOE) gene is associated with progression of age-related macular degeneration (AMD). Hum. Mutat. 27:4337–42 [Google Scholar]
  11. Beazley-Long N, Hua J, Jehle T, Hulse RP, Dersch R. et al. 2013. VEGF-A165b is an endogenous neuroprotective splice isoform of vascular endothelial growth factor A in vivo and in vitro. Am. J. Pathol. 183:3918–29 [Google Scholar]
  12. Bindewald A, Schmitz-Valckenberg S, Jorzik JJ, Dolar-Szczasny J, Sieber H. et al. 2005. Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration. Br. J. Ophthalmol. 89:7874–78 [Google Scholar]
  13. Birch DG, Liang FQ. 2007. Age-related macular degeneration: a target for nanotechnology derived medicines. Int. J. Nanomed. 2:165–77 [Google Scholar]
  14. Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G. et al. 1995. An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv. Ophthalmol. 39:5367–74 [Google Scholar]
  15. Booij JC, Baas DC, Beisekeeva J, Gorgels TGMF, Bergen AAB. 2010. The dynamic nature of Bruch's membrane. Prog. Retin. Eye Res. 29:11–18 [Google Scholar]
  16. Bowes Rickman C, Farsiu S, Toth CA, Klingeborn M. 2013. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging. Investig. Ophthalmol. Vis. Sci. 54:14ORSF68–80 [Google Scholar]
  17. Boyle AP, Hong EL, Hariharan M, Cheng Y, Schaub MA. et al. 2012. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22:91790–97 [Google Scholar]
  18. Brandl C, Grassmann F, Riolfi J, Weber BHF. 2015. Tapping stem cells to target AMD - challenges and prospects. J. Clin. Med. 4:282–303 [Google Scholar]
  19. Brandl C, Zimmermann SJ, Milenkovic VM, Rosendahl SMG, Grassmann F. et al. 2014. In-depth characterisation of Retinal Pigment Epithelium (RPE) cells derived from human induced pluripotent stem cells (hiPSC). NeuroMol. Med. 16:3551–64 [Google Scholar]
  20. Buchholz DE, Pennington BO, Croze RH, Hinman CR, Coffey PJ, Clegg DO. 2013. Rapid and efficient directed differentiation of human pluripotent stem cells into retinal pigmented epithelium. Stem Cells Transl. Med. 2:5384–93 [Google Scholar]
  21. Buitendijk GHS, Rochtchina E, Myers C, van Duijn CM, Lee KE. et al. 2013. Prediction of age-related macular degeneration in the general population: the Three Continent AMD Consortium. Ophthalmology 120:122644–55 [Google Scholar]
  22. Caire J, Recalde S, Velazquez-Villoria A, Garcia-Garcia L, Reiter N. et al. 2014. Growth of geographic atrophy on fundus autofluorescence and polymorphisms of CFH, CFB, C3, FHR1-3, and ARMS2 in age-related macular degeneration. JAMA Ophthalmol. 2014:528–34 [Google Scholar]
  23. Chakravarthy U, Wong TY, Fletcher A, Piault E, Evans C. et al. 2010. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol. 10:131 [Google Scholar]
  24. Coetzee SG, Rhie SK, Berman BP, Coetzee GA, Noushmehr H. 2012. FunciSNP: an R/bioconductor tool integrating functional non-coding data sets with genetic association studies to identify candidate regulatory SNPs. Nucleic Acids Res. 40:18e139 [Google Scholar]
  25. Coleman HR, Chan C-C, Ferris FL, Chew EY. 2008. Age-related macular degeneration. Lancet 372:96521835–45 [Google Scholar]
  26. Crabb JW, Miyagi M, Gu X, Shadrach K, West KA. et al. 2002. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. PNAS 99:2314682–87 [Google Scholar]
  27. Curcio CA, Johnson M, Huang J-D, Rudolf M. 2010. Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration. J. Lipid Res. 51:3451–67 [Google Scholar]
  28. Curcio CA, Medeiros NE, Millican CL. 1998. The Alabama Age-Related Macular Degeneration Grading System for donor eyes. Investig. Ophthalmol. Vis. Sci. 39:71085–96 [Google Scholar]
  29. Curcio CA, Messinger JD, Sloan KR, McGwin G, Medeiros NE, Spaide RF. 2013. Subretinal drusenoid deposits in non-neovascular age-related macular degeneration: morphology, prevalence, topography, and biogenesis model. Retina 33:2265–76 [Google Scholar]
  30. Curcio CA, Millican CL. 1999. Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch. Ophthalmol. 117:3329–39 [Google Scholar]
  31. Curcio CA, Millican CL, Allen KA, Kalina RE. 1993. Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Investig. Ophthalmol. Vis. Sci. 34:123278–96 [Google Scholar]
  32. Curcio CA, Presley JB, Malek G, Medeiros NE, Avery DV, Kruth HS. 2005a. Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy. Exp. Eye Res. 81:6731–41 [Google Scholar]
  33. Curcio CA, Presley JB, Millican CL, Medeiros NE. 2005b. Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles. Exp. Eye Res. 80:6761–75 [Google Scholar]
  34. Edwards SL, Beesley J, French JD, Dunning AM. 2013. Beyond GWASs: illuminating the dark road from association to function. Am. J. Hum. Genet. 93:5779–97 [Google Scholar]
  35. Feeney L. 1978. Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies. Investig. Ophthalmol. Vis. Sci. 17:7583–600 [Google Scholar]
  36. Feeney-Burns L, Ellersieck MR. 1985. Age-related changes in the ultrastructure of Bruch's membrane. Am. J. Ophthalmol. 100:5686–97 [Google Scholar]
  37. Feeney-Burns L, Hilderbrand ES, Eldridge S. 1984. Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Investig. Ophthalmol. Vis. Sci. 25:2195–200 [Google Scholar]
  38. Ferris FL, Davis MD, Clemons TE, Lee L-Y, Chew EY. et al. 2005. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch. Ophthalmol. 123:111570–74 [Google Scholar]
  39. Ferris FL, Wilkinson CP, Bird A, Chakravarthy U, Chew E. et al. 2013. Clinical classification of age-related macular degeneration. Ophthalmology 120:4844–51 [Google Scholar]
  40. Forrest ARR, Kawaji H, Rehli M, Baillie JK, de Hoon MJL. et al. 2014. A promoter-level mammalian expression atlas. Nature 507:7493462–70 [Google Scholar]
  41. Fritsche LG, Chen W, Schu M, Yaspan BL, Yu Y. et al. 2013. Seven new loci associated with age-related macular degeneration. Nat. Genet. 45:4433–39 [Google Scholar]
  42. Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A. 2014. Age-related macular degeneration: genetics and biology coming together. Annu. Rev. Genomics Hum. Genet. 15:151–71 [Google Scholar]
  43. Fritsche LG, Fleckenstein M, Fiebig BS, Schmitz-Valckenberg S, Bindewald-Wittich A. et al. 2012. A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene. Investig. Ophthalmol. Vis. Sci. 53:42112–18 [Google Scholar]
  44. Gao H, Hollyfield JG. 1992. Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells. Investig. Ophthalmol. Vis. Sci. 33:11–17 [Google Scholar]
  45. Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA. et al. 2006. Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry 63:2168–74 [Google Scholar]
  46. Godara P, Siebe C, Rha J, Michaelides M, Carroll J. 2010. Assessing the photoreceptor mosaic over drusen using adaptive optics and SD-OCT. Ophthalmic Surg. Lasers Imaging 41:S104–8 [Google Scholar]
  47. Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ. et al. 2006. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat. Genet. 38:4458–62 [Google Scholar]
  48. Gorin MB. 2012. Genetic insights into age-related macular degeneration: controversies addressing risk, causality, and therapeutics. Mol. Aspects Med. 33:4467–86 [Google Scholar]
  49. Gorski M, Winkler TW, Stark K, Müller-Nurasyid M, Ried JS. et al. 2014. Harmonization of study and reference data by PhaseLift: saving time when imputing study data. Genet. Epidemiol. 38:5381–88 [Google Scholar]
  50. Grassmann F, Heid IM, Weber BHF. 2014. Genetic risk models in age-related macular degeneration. Adv. Exp. Med. Biol. 801:291–300 [Google Scholar]
  51. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ. et al. 2005. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. PNAS 102:207227–32 [Google Scholar]
  52. Hammond CJ, Webster AR, Snieder H, Bird AC, Gilbert CE, Spector TD. 2002. Genetic influence on early age-related maculopathy: a twin study. Ophthalmology 109:4730–36 [Google Scholar]
  53. Hogg RE, Silva R, Staurenghi G, Murphy G, Santos AR. et al. 2014. Clinical characteristics of reticular pseudodrusen in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Ophthalmology 121:91748–55 [Google Scholar]
  54. Holliday EG, Smith AV, Cornes BK, Buitendijk GHS, Jensen RA. et al. 2013. Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis. PLOS ONE 8:1e53830 [Google Scholar]
  55. Holz FG, Bindewald-Wittich A, Fleckenstein M, Dreyhaupt J, Scholl HPN, Schmitz-Valckenberg S. 2007. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am. J. Ophthalmol. 143:3463–72 [Google Scholar]
  56. Holz FG, Schmitz-Valckenberg S, Fleckenstein M. 2014. Recent developments in the treatment of age-related macular degeneration. J. Clin. Investig. 124:41430–38 [Google Scholar]
  57. Jackson GR, Owsley C, Curcio CA. 2002. Photoreceptor degeneration and dysfunction in aging and age-related maculopathy. Ageing Res. Rev. 1:3381–96 [Google Scholar]
  58. 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. 77:3389–407 [Google Scholar]
  59. Johnson LV, Ozaki S, Staples MK, Erickson PA, Anderson DH. 2000. A potential role for immune complex pathogenesis in drusen formation. Exp. Eye Res. 70:4441–49 [Google Scholar]
  60. Kamei M, Hollyfield JG. 1999. TIMP-3 in Bruch's membrane: changes during aging and in age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 40:102367–75 [Google Scholar]
  61. Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A. et al. 2014. Defining functional DNA elements in the human genome. PNAS 111:176131–38 [Google Scholar]
  62. Killingsworth MC. 1995. Angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch. Clin. Exp. Ophthalmol. 233:6313–23 [Google Scholar]
  63. Kim C. 2014. Disease modeling and cell based therapy with iPSC: future therapeutic option with fast and safe application. Blood Res. 49:17–14 [Google Scholar]
  64. Kjeldsen MJ, Kyvik KO, Christensen K, Friis ML. 2001. Genetic and environmental factors in epilepsy: a population-based study of 11,900 Danish twin pairs. Epilepsy Res. 44:2–3167–78 [Google Scholar]
  65. Klaver CCW, Kliffen M, van Duijn CM, Hofman A, Cruts M. et al. 1998. Genetic association of apolipoprotein E with age-related macular degeneration. Ophthalmic Res.200–206
  66. Klein ML, Ferris FL III, Francis PJ, Lindblad AS, Chew EY. et al. 2010. Progression of geographic atrophy and genotype in age-related macular degeneration. Ophthalmology 117:81554–1559.e1 [Google Scholar]
  67. Klein R, Davis MD, Magli YL, Segal P, Klein BEK, Hubbard L. 1991. The Wisconsin age-related maculopathy grading system. Ophthalmology 98:71128–34 [Google Scholar]
  68. Klein R, Klein BEK, Jensen SC, Meuer SM. 1997. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 104:17–21 [Google Scholar]
  69. Klein R, Klein BEK, Knudtson MD, Meuer SM, Swift M, Gangnon RE. 2007. Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 114:2253–62 [Google Scholar]
  70. Klein R, Meuer SM, Myers CE, Buitendijk GHS, Rochtchina E. et al. 2014. Harmonizing the classification of age-related macular degeneration in the Three-Continent AMD Consortium. Ophthalmic Epidemiol. 21:114–23 [Google Scholar]
  71. Klein RJ, Zeiss C, Chew EY, Tsai J-Y, Sackler RS. et al. 2005. Complement factor H polymorphism in age-related macular degeneration. Science 308:5720385–89 [Google Scholar]
  72. Kraft P, Cox DG. 2008. Study designs for genome-wide association studies. Adv. Genet. 60:465–504 [Google Scholar]
  73. Krohne TU, Westenskow PD, Kurihara T, Friedlander DF, Lehmann M. et al. 2012. Generation of retinal pigment epithelial cells from small molecules and OCT4 reprogrammed human induced pluripotent stem cells. Stem Cells Transl. Med. 1:296–109 [Google Scholar]
  74. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R. et al. 2013. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet. 45:121452–58 [Google Scholar]
  75. Lefrançois P, Zheng W, Snyder M. 2010. ChIP-Seq: using high-throughput DNA sequencing for genome-wide identification of transcription factor binding sites. Methods Enzymol. 470:77–104 [Google Scholar]
  76. Liang L, Morar N, Dixon AL, Lathrop GM, Abecasis GR. et al. 2013. A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines. Genome Res. 23:4716–26 [Google Scholar]
  77. Magnusson KP, Duan S, Sigurdsson H, Petursson H, Yang Z. et al. 2006. CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD. PLOS Med. 3:1e5 [Google Scholar]
  78. Malek G, Li C-M, Guidry C, Medeiros NE, Curcio CA. 2003. Apolipoprotein B in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. Am. J. Pathol. 162:2413–25 [Google Scholar]
  79. Marshall GE, Konstas AGP, Reid GG, Edwards JG, Lee WR. 1992. Type IV collagen and laminin in Bruch's membrane and basal linear deposit in the human macula. Br. J. Ophthalmol. 76:10607–14 [Google Scholar]
  80. McKay GJ, Silvestri G, Chakravarthy U, Dasari S, Fritsche LG. et al. 2011. Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people. Am. J. Epidemiol. 173:121357–64 [Google Scholar]
  81. Moore DJ, Hussain AA, Marshall J. 1995. Age-related variation in the hydraulic conductivity of Bruch's membrane. Investig. Ophthalmol. Vis. Sci. 36:71290–97 [Google Scholar]
  82. Mrejen S, Sato T, Curcio CA, Spaide RF. 2014. Assessing the cone photoreceptor mosaic in eyes with pseudodrusen and soft drusen in vivo using adaptive optics imaging. Ophthalmology 121:2545–51 [Google Scholar]
  83. 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. 14:7835–46 [Google Scholar]
  84. Nociari MM, Lehmann GL, Perez Bay AE, Radu RA, Jiang Z. et al. 2014. Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium. PNAS 111:14E1402–8 [Google Scholar]
  85. Olsen TW, Feng X. 2004. The Minnesota Grading System of eye bank eyes for age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 45:124484–90 [Google Scholar]
  86. Parameswaran S, Balasubramanian S, Babai N, Qiu F, Eudy JD. et al. 2010. Induced pluripotent stem cells generate both retinal ganglion cells and photoreceptors: therapeutic implications in degenerative changes in glaucoma and age-related macular degeneration. Stem Cells 28:4695–703 [Google Scholar]
  87. Pe’er J, Shweiki D, Itin A, Hemo I, Gnessin H, Keshet E. 1995. Hypoxia-induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab. Investig. 72:6638–45 [Google Scholar]
  88. Pennesi ME, Neuringer M, Courtney RJ. 2012. Animal models of age related macular degeneration. Mol. Aspects Med. 33:4487–509 [Google Scholar]
  89. Ramrattan RS, van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, de Jong PT. 1994. Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging. Investig. Ophthalmol. Vis. Sci. 35:62857–64 [Google Scholar]
  90. Randall JC, Winkler TW, Kutalik Z, Berndt SI, Jackson AU. et al. 2013. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLOS Genet. 9:6e1003500 [Google Scholar]
  91. Rivera A, Fisher SA, Fritsche LG, Keilhauer CN, Lichtner P. et al. 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. 14:213227–36 [Google Scholar]
  92. Rivera A, White K, Stöhr H, Steiner K, Hemmrich N. et al. 2000. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. Am. J. Hum. Genet. 67:4800–13 [Google Scholar]
  93. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K. 2013. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology 120:112292–99 [Google Scholar]
  94. Rudolf M, Clark ME, Chimento MF, Li C-M, Medeiros NE, Curcio CA. 2008. Prevalence and morphology of druse types in the macula and periphery of eyes with age-related maculopathy. Investig. Ophthalmol. Vis. Sci. 49:31200–9 [Google Scholar]
  95. Rudolf M, Curcio CA. 2009. Esterified cholesterol is highly localized to Bruch's membrane, as revealed by lipid histochemistry in wholemounts of human choroid. J. Histochem. Cytochem. 57:8731–39 [Google Scholar]
  96. Sarks JP, Sarks SH, Killingsworth MC. 1988. Evolution of geographic atrophy of the retinal pigment epithelium. Eye 2:552–77 [Google Scholar]
  97. Sarks JP, Sarks SH, Killingsworth MC. 1997. Morphology of early choroidal neovascularisation in age-related macular degeneration: correlation with activity. Eye 11:515–22 [Google Scholar]
  98. Sarks S, Cherepanoff S, Killingsworth M, Sarks J. 2007. Relationship of basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 48:3968–77 [Google Scholar]
  99. Sarks SH. 1976. Ageing and degeneration in the macular region: a clinico-pathological study. Br. J. Ophthalmol. 60:5324–41 [Google Scholar]
  100. Sarks SH. 1982. Drusen patterns predisposing to geographic atrophy of the retinal pigment epithelium. Aust. J. Ophthalmol. 10:291–97 [Google Scholar]
  101. Sarks SH, Arnold JJ, Killingsworth MC, Sarks JP. 1999. Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study. Br. J. Ophthalmol. 83:3358–68 [Google Scholar]
  102. Schmitz-Valckenberg S, Alten F, Steinberg JS, Jaffe GJ, Fleckenstein M. et al. 2011. Reticular drusen associated with geographic atrophy in age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 52:95009–15 [Google Scholar]
  103. Scholl HPN, Fleckenstein M, Fritsche LG, Schmitz-Valckenberg S, Göbel A. et al. 2009. CFH, C3 and ARMS2 are significant risk loci for susceptibility but not for disease progression of geographic atrophy due to AMD. PLOS ONE 4:10e7418 [Google Scholar]
  104. 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. 123:3321–27 [Google Scholar]
  105. Seddon JM, Reynolds R, Maller J, Fagerness JA, Daly MJ, Rosner B. 2009. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Investig. Ophthalmol. Vis. Sci. 50:52044–53 [Google Scholar]
  106. Seddon JM, Sharma S, Adelman RA. 2006. Evaluation of the clinical age-related maculopathy staging system. Ophthalmology 113:2260–66 [Google Scholar]
  107. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA. et al. 2014. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343:616684–87 [Google Scholar]
  108. Sifrim A, Van Houdt JKJ, Tranchevent L-C, Nowakowska B, Sakai R. et al. 2012. Annotate-it: a Swiss-knife approach to annotation, analysis and interpretation of single nucleotide variation in human disease. Genome Med. 4:973 [Google Scholar]
  109. Singh R, Phillips MJ, Kuai D, Meyer J, Martin JM. et al. 2013a. Functional analysis of serially expanded human iPS cell-derived RPE cultures. Investig. Ophthalmol. Vis. Sci. 54:106767–78 [Google Scholar]
  110. Singh R, Shen W, Kuai D, Martin JM, Guo X. et al. 2013b. iPS cell modeling of Best disease: insights into the pathophysiology of an inherited macular degeneration. Hum. Mol. Genet. 22:3593–607 [Google Scholar]
  111. Sivaprasad S, Bailey TA, Chong VNH. 2005. Bruch's membrane and the vascular intima: Is there a common basis for age-related changes and disease?. Clin. Exp. Ophthalmol. 33:5518–23 [Google Scholar]
  112. Skerka C, Lauer N, Weinberger AAWA, Keilhauer CN, Sünhel J. et al. 2007. Defective complement control of Factor H (Y402H) and FHL-1 in age-related macular degeneration. Mol. Immunol. 44:3398–3406 [Google Scholar]
  113. Smith AG, Kaiser PK. 2014. Emerging treatments for wet age-related macular degeneration. Expert Opin. Emerg. Drugs. 19:1157–64 [Google Scholar]
  114. Spaide RF. 2009. Age-related choroidal atrophy. Am. J. Ophthalmol. 147:5801–10 [Google Scholar]
  115. Spaide RF, Armstrong D, Browne R. 2003. Choroidal neovascularization in age-related macular degeneration—what is the cause?. Retina 23:5595–614 [Google Scholar]
  116. Spaide RF, Curcio CA, Zweifel SA. 2010. Drusen, an old but new frontier. Retina 30:81163–65 [Google Scholar]
  117. Spencer KL, Olson LM, Anderson BM, Schnetz-Boutaud N, Scott WK. et al. 2008. C3 R102G polymorphism increases risk of age-related macular degeneration. Hum. Mol. Genet. 17:121821–24 [Google Scholar]
  118. Spraul CW, Grossniklaus HE. 1997. Characteristics of drusen and Bruch's membrane in postmortem eyes with age-related macular degeneration. Arch. Ophthalmol. 115:2267–73 [Google Scholar]
  119. Spraul CW, Lang GE, Grossniklaus HE, Lang GK. 1999. Histologic and morphometric analysis of the choroid, Bruch's membrane, and retinal pigment epithelium in postmortem eyes with age-related macular degeneration and histologic examination of surgically excised choroidal neovascular membranes. Surv. Ophthalmol. 44:S10–32 [Google Scholar]
  120. Stone EM, Webster AR, Vandenburgh K, Streb LM, Hockey RR. et al. 1998. Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration. Nat. Genet. 20:4328–29 [Google Scholar]
  121. Strauss O. 2005. The retinal pigment epithelium in visual function. Physiol. Rev. 85:3845–81 [Google Scholar]
  122. Suzuki M, Sato T, Spaide RF. 2014. Pseudodrusen subtypes as delineated by multimodal imaging of the fundus. Am. J. Ophthalmol. 157:51005–12 [Google Scholar]
  123. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T. et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:5861–72 [Google Scholar]
  124. Teo YY, Small KS. 2010. A novel method for haplotype clustering and visualization. Genet. Epidemiol. 34:134–41 [Google Scholar]
  125. Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE. et al. 2012. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet. 44:121341–48 [Google Scholar]
  126. Tysk C, Lindberg E, Järnerot G, Flodérus-Myrhed B. 1988. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut 29:7990–96 [Google Scholar]
  127. van der Schaft TL, Mooy CM, de Bruijn WC, Bosman FT, de Jong PT. 1994. Immunohistochemical light and electron microscopy of basal laminar deposit. Graefes Arch. Clin. Exp. Ophthalmol. 232:140–46 [Google Scholar]
  128. Walley AJ, Blakemore AIF, Froguel P. 2006. Genetics of obesity and the prediction of risk for health. Hum. Mol. Genet. 15:R124–30 [Google Scholar]
  129. Wang J, Duncan D, Shi Z, Zhang B. 2013. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 41:W77–83 [Google Scholar]
  130. Wang L, Li C-M, Rudolf M, Belyaeva OV, Chung BH. et al. 2009. Lipoprotein particles of intraocular origin in human Bruch membrane: an unusual lipid profile. Investig. Ophthalmol. Vis. Sci. 50:2870–77 [Google Scholar]
  131. Wang T, Wei JJ, Sabatini DM, Lander ES. 2014. Genetic screens in human cells using the CRISPR-Cas9 system. Science 343:616680–84 [Google Scholar]
  132. Weber BHF, Charbel Issa P, Pauly D, Herrmann P, Grassmann F, Holz FG. 2014. The role of the complement system in age-related macular degeneration. Dtsch. Ärztebl. Int. 111:8133–38 [Google Scholar]
  133. Welter D, MacArthur J, Morales J, Burdett T, Hall P. et al. 2014. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 42:D1001–6 [Google Scholar]
  134. Westenskow PD, Kurihara T, Friedlander M. 2014. Utilizing stem cell-derived RPE cells as a therapeutic intervention for age-related macular degeneration. Adv. Exp. Med. Biol. 801:323–29 [Google Scholar]
  135. Williams MA, McKay GJ, Chakravarthy U. 2014. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst. Rev. 1:CD009300 [Google Scholar]
  136. Wu Z, Luu CD, Ayton LN, Goh JK, Lucci LM. et al. 2014. Optical coherence tomography–defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration. Ophthalmology 121:2415–22 [Google Scholar]
  137. Yamanaka S. 2012. Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 10:6678–84 [Google Scholar]
  138. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL. et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:58581917–20 [Google Scholar]
  139. Yu Y, Bhangale TR, Fagerness J, Ripke S, Thorleifsson G. et al. 2011. Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. Hum. Mol. Genet. 20:183699–3709 [Google Scholar]
  140. Zarbin MA, Casaroli-Marano RP, Rosenfeld PJ. 2014. Age-related macular degeneration: clinical findings, histopathology and imaging techniques. Dev. Ophthalmol. 53:1–32 [Google Scholar]
  141. Zareparsi S, Reddick AC, Branham KEH, Moore KB, Jessup L. et al. 2004. Association of apolipoprotein E alleles with susceptibility to age-related macular degeneration in a large cohort from a single center. Investig. Ophthalmol. Vis. Sci. 45:51306–10 [Google Scholar]
  142. Zhang F, Wen Y, Guo X. 2014. CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum. Mol. Genet. 23:R1R40–46 [Google Scholar]
  143. Zhang Y, Wang X, Rivero EB, Clark ME, Witherspoon CD. et al. 2014. Photoreceptor perturbation around subretinal drusenoid deposits as revealed by adaptive optics scanning laser ophthalmoscopy. Am. J. Ophthalmol. 158:3584–96.e1 [Google Scholar]
  144. Zhou T, Benda C, Dunzinger S, Huang Y, Ho JC. et al. 2012. Generation of human induced pluripotent stem cells from urine samples. Nat. Protoc. 7:122080–89 [Google Scholar]
  145. Zhou Y, Zeng F. 2013. Integration-free methods for generating induced pluripotent stem cells. Genomics Proteomics Bioinform. 11:5284–87 [Google Scholar]
  146. Zou F, Chai HS, Younkin CS, Allen M, Crook J. et al. 2012. Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants. PLOS Genet. 8:6e1002707 [Google Scholar]
  147. Zweifel SA, Spaide RF, Curcio CA, Malek G, Imamura Y. 2010. Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology 117:2303–12.e1 [Google Scholar]
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