Age-Related Macular Degeneration

  • Sam Khandhadia
  • Jocelyn Cherry
  • Andrew John Lotery
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 724)

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Despite recent advances in treatment, AMD causes considerable morbidity. For the non-ophthalmologist, a brief background on retinal structure is provided, followed by a description of the characteristic changes seen in AMD. Subsequently the typical clinical features of AMD are discussed with an outline of present management, followed by the current theories of AMD pathogenesis. The similarities between AMD and another neurodegenerative disease are then highlighted. Finally, we review the on-going clinical trials of potential treatments for the future. Since it is clear that multiple risk factors are involved in the pathogenesis of AMD, a multi-faceted approach will most likely be required in order to prevent further patients progressing to blindness as a result of this devastating condition.

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References

  1. 1.
    Resnikoff S, Pascolini D, Etya’ale D et al. Global data on visual impairment in the year 2002. Bull World Health Organ 2004; 82:844–851.PubMedGoogle Scholar
  2. 2.
    Klein R, Cruickshanks KJ, Nash SD et al. The prevalence of age-related macular degeneration and associated risk factors. Arch Ophthalmol 2010; 128:750–758.PubMedCrossRefGoogle Scholar
  3. 3.
    Friedman DS, O’Colmain BJ, Munoz B et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004; 122:564–572.PubMedCrossRefGoogle Scholar
  4. 4.
    de Jong PT. Age-related macular degeneration. N Engl J Med 2006; 355:1474–1485.PubMedCrossRefGoogle Scholar
  5. 5.
    Seland JH, Vingerling JR, Augood CA et al. Visual Impairment and quality of life in the Older European Population, the EUREYE study. Acta Ophthalmol 2009.Google Scholar
  6. 6.
    Klein R, Klein BE, Knudtson MD et al. Prevalence of age-related macular degeneration in 4 racial/ethnic groups in the multi-ethnic study of atherosclerosis. Ophthalmology 2006; 113:373–380.PubMedCrossRefGoogle Scholar
  7. 7.
    Klein R, Klein BE, Jensen SC et al. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 1997; 104:7–21.PubMedGoogle Scholar
  8. 8.
    Jonas JB, Schneider U, Naumann GO. Count and density of human retinal photoreceptors. Graefes Arch Clin Exp Ophthalmol 1992; 230:505–510.PubMedCrossRefGoogle Scholar
  9. 9.
    Ryan SJ, Ryan SJ. Retina 4th Ed, Elsevier/Mosby, Philadelphia, Pa, USA. Retina. 2006. Philadelphia, Pa.: Elsevier/Mosby.Google Scholar
  10. 10.
    Boulton M, Dayhaw-Barker P. The role of the retinal pigment epithelium: topographical variation and ageing changes. Eye 2001; 15:3–9.CrossRefGoogle Scholar
  11. 11.
    Johnson LV, Leitner WP, Staples MK et al. Complement activation and inflammatory processes in Drusen formation and age related macular degeneration. Exp Eye Res 2001; 73:887–896.PubMedCrossRefGoogle Scholar
  12. 12.
    Mullins RF, Russell SR, Anderson DH et al. 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; 14:835–846.PubMedGoogle Scholar
  13. 13.
    Klein R, Meuer SM, Knudtson MD et al. The epidemiology of retinal reticular drusen. Am J Ophthalmol 2008; 145:317–326.PubMedCrossRefGoogle Scholar
  14. 14.
    Knudtson MD, Klein R, Klein BE et al. Location of lesions associated with age-related maculopathy over a 10-year period: the Beaver Dam Eye Study. Invest Ophthalmol Vis Sci 2004; 45:2135–2142.PubMedCrossRefGoogle Scholar
  15. 15.
    Augood CA, Vingerling JR, de Jong PT et al. Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE). Arch Ophthalmol 2006; 124:529–535.PubMedCrossRefGoogle Scholar
  16. 16.
    Brown DM, Kaiser PK, Michels M et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006; 355:1432–1444.PubMedCrossRefGoogle Scholar
  17. 17.
    Rosenfeld PJ, Brown DM, Heier JS et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355:1419–1431.PubMedCrossRefGoogle Scholar
  18. 18.
    Lalwani GA, Rosenfeld PJ, Fung AE et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol 2009; 148:43–58.PubMedCrossRefGoogle Scholar
  19. 19.
    Hassan AS, Johnson MW, Schneiderman TE et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology 1999; 106:1900–1906.PubMedCrossRefGoogle Scholar
  20. 20.
    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.[Erratum appears in Arch Ophthalmol. 2008;126(9):1251]. Arch Ophthalmol 2001; 119:1417–1436.Google Scholar
  21. 21.
    Montgomery MP, Kamel F, Pericak-Vance MA et al. Overall diet quality and age-related macular degeneration. Ophthalmic Epidemiol 2010; 17:58–65.PubMedCrossRefGoogle Scholar
  22. 22.
    Augood C, Chakravarthy U, Young I et al. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes and associations with neovascular age-related macular degeneration. Am J Clin Nutr 2008; 88:398–406.PubMedGoogle Scholar
  23. 23.
    Cho E, Seddon JM, Rosner B et al. Prospective study of intake of fruits, vegetables, vitamins and carotenoids and risk of age-related maculopathy. Arch Ophthalmol 2004; 122:883–892.PubMedCrossRefGoogle Scholar
  24. 24.
    Khan JC, Thurlby DA, Shahid H et al. Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation. Br J Ophthalmol 2006; 90:75–80.PubMedCrossRefGoogle Scholar
  25. 25.
    Klein R, Klein BE, Linton KL et al. The Beaver Dam Eye Study: the relation of age-related maculopathy to smoking. Am J Epidemiol 1993; 137:190–200.PubMedGoogle Scholar
  26. 26.
    Hogg RE, Woodside JV, Gilchrist SE et al. Cardiovascular disease and hypertension are strong risk factors for choroidal neovascularization. Ophthalmology 2008; 115:1046–1052.PubMedCrossRefGoogle Scholar
  27. 27.
    Klein R, Klein BE, Tomany SC et al. The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 2003; 110:1273–1280.PubMedCrossRefGoogle Scholar
  28. 28.
    Peeters A, Magliano DJ, Stevens J et al. Changes in abdominal obesity and age-related macular degeneration: the Atherosclerosis Risk in Communities Study. Arch Ophthalmol 2008; 126:1554–1560.PubMedCrossRefGoogle Scholar
  29. 29.
    Tomany SC, Cruickshanks KJ, Klein R et al. Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye Study. Arch Ophthalmol 2004; 122:750–757.PubMedCrossRefGoogle Scholar
  30. 30.
    Cruickshanks KJ, Klein R, Klein BE. Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. Arch Ophthalmol 1993; 111:514–518.PubMedCrossRefGoogle Scholar
  31. 31.
    Fletcher AE, Bentham GC, Agnew M et al. Sunlight exposure, antioxidants and age-related macular degeneration. Arch Ophthalmol 2008; 126:1396–1403.PubMedCrossRefGoogle Scholar
  32. 32.
    Laser treatment in patients with bilateral large drusen: the complications of age-related macular degeneration prevention trial. Ophthalmology 2006; 113:1974–1986.Google Scholar
  33. 33.
    Giansanti F, Eandi CM, Virgili G. Submacular surgery for choroidal neovascularisation secondary to age-related macular degeneration. Cochrane Database Syst Rev 2009; CD006931.Google Scholar
  34. 34.
    Pauleikhoff D, Radermacher M, Spital G et al. Visual prognosis of second eyes in patients with unilateral late exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2002; 240:539–542.PubMedCrossRefGoogle Scholar
  35. 35.
    Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 1992; 99:933–943.PubMedGoogle Scholar
  36. 36.
    Maguire P, Vine AK. Geographic atrophy of the retinal pigment epithelium. Am J Ophthalmol 1986; 102:621–625.PubMedGoogle Scholar
  37. 37.
    Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium. Eye (Lond) 1988; 2 (Pt 5):552–577.CrossRefGoogle Scholar
  38. 38.
    Swaroop A, Chew EY, Rickman CB et al. Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. Annu Rev Genomics Hum Genet 2009; 10:19–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Yoshida S, Yashar BM, Hiriyanna S et al. Microarray analysis of gene expression in the aging human retina. Invest Ophthalmol Vis Sci 2002; 43:2554–2560.PubMedGoogle Scholar
  40. 40.
    Katz ML, Robison WG Jr. Age-related changes in the retinal pigment epithelium of pigmented rats. Exp Eye Res 1984; 38:137–151.PubMedCrossRefGoogle Scholar
  41. 41.
    Wing GL, Blanchard GC, Weiter JJ. The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 1978; 17:601–607.PubMedGoogle Scholar
  42. 42.
    Iwasaki M, Inomata H. Lipofuscin granules in human photoreceptor cells. Invest Ophthalmol Vis Sci 1988; 29:671–679.PubMedGoogle Scholar
  43. 43.
    Ng KP, Gugiu B, Renganathan K et al. Retinal pigment epithelium lipofuscin proteomics. Molecular and Cellular Proteomics 2008; 7:1397–1405.PubMedCrossRefGoogle Scholar
  44. 44.
    Sparrow JR, Vollmer-Snarr HR, Zhou J et al. A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formation. Journal of Biological Chemistry 2003; 278:18207–18213.PubMedCrossRefGoogle Scholar
  45. 45.
    Zhou J, Kim SR, Westlund BS et al. Complement activation by bisretinoid constituents of RPE lipofuscin. Investigative Ophthalmology and Visual Science 2009; 50:1392–1399.PubMedCrossRefGoogle Scholar
  46. 46.
    Tsutsumi-Miyahara C, Sonoda KH, Egashira K et al. The relative contributions of each subset of ocular infiltrated cells in experimental choroidal neovascularisation. Br J Ophthalmol 2004; 88:1217–1222.PubMedCrossRefGoogle Scholar
  47. 47.
    Klein RJ, Zeiss C, Chew EY et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005; 308:385–389.PubMedCrossRefGoogle Scholar
  48. 48.
    Haines JL, Hauser MA, Schmidt S et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 2005; 308:419–421.PubMedCrossRefGoogle Scholar
  49. 49.
    Edwards AO, Ritter R III, Abel KJ et al. Complement factor H polymorphism and age-related macular degeneration. Science 2005; 308:421–424.PubMedCrossRefGoogle Scholar
  50. 50.
    Yates JR, Sepp T, Matharu BK et al. Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med 2007; 357:553–561.PubMedCrossRefGoogle Scholar
  51. 51.
    Gold B, Merriam JE, Zernant J et al. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet 2006; 38:458–462.PubMedCrossRefGoogle Scholar
  52. 52.
    Ennis S, Gibson J, Cree AJ et al. Support for the involvement of complement factor I in age-related macular degeneration. Eur J Hum Genet 2009.Google Scholar
  53. 53.
    Fagerness JA, Maller JB, Neale BM et al. Variation near complement factor I is associated with risk of advanced AMD. Eur J Hum Genet 2009; 17:100–104.PubMedCrossRefGoogle Scholar
  54. 54.
    Hageman GS, Hancox LS, Taiber AJ et al. Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann Med 2006; 38:592–604.PubMedCrossRefGoogle Scholar
  55. 55.
    Hughes AE, Orr N, Esfandiary H et al. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat Genet 2006; 38:1173–1177.PubMedCrossRefGoogle Scholar
  56. 56.
    Ennis S, Jomary C, Mullins R et al. Association between the SERPING1 gene and age-related macular degeneration: a two-stage case-control study. Lancet 2008.Google Scholar
  57. 57.
    Baudouin C, Peyman GA, Fredj-Reygrobellet D et al. Immunohistological study of subretinal membranes in age-related macular degeneration. Jpn J Ophthalmol 1992; 36:443–451.PubMedGoogle Scholar
  58. 58.
    Goverdhan SV, Howell MW, Mullins RF et al. Association of HLA class I and class II polymorphisms with age-related macular degeneration. Investigative Ophthalmology and Visual Science 46(5):1726–34, 2005.PubMedCrossRefGoogle Scholar
  59. 59.
    Cho Y, Wang JJ, Chew EY et al. Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci 2009; 50:5614–5618.PubMedCrossRefGoogle Scholar
  60. 60.
    Yang Z, Stratton C, Francis PJ et al. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N Engl J Med 2008; 359:1456–1463.PubMedCrossRefGoogle Scholar
  61. 61.
    Robman L, Mahdi O, McCarty C et al. Exposure to Chlamydia pneumoniae infection and progression of age-related macular degeneration. Am J Epidemiol 2005; 161:1013–1019.PubMedCrossRefGoogle Scholar
  62. 62.
    Kalayoglu MV, Galvan C, Mahdi OS et al. Serological association between Chlamydia pneumoniae infection and age-related macular degeneration. Arch Ophthalmol 2003; 121:478–482.PubMedCrossRefGoogle Scholar
  63. 63.
    Robman L, Mahdi OS, Wang JJ et al. Exposure to Chlamydia pneumoniae infection and age-related macular degeneration: the Blue Mountains Eye Study. Invest Ophthalmol Vis Sci 2007; 48:4007–4011.PubMedCrossRefGoogle Scholar
  64. 64.
    Kanda A, Chen W, Othman M et al. A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci USA 2007; 104:16227–16232.PubMedCrossRefGoogle Scholar
  65. 65.
    Fritsche LG, Loenhardt T, Janssen A et al. Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet 2008; 40:892–896.PubMedCrossRefGoogle Scholar
  66. 66.
    Wang G, Spencer KL, Court BL et al. Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria. Invest Ophthalmol Vis Sci 2009; 50:3084–3090.PubMedCrossRefGoogle Scholar
  67. 67.
    National Eye Institute (NEI). Age-Related Eye Disease Study 2 (AREDS2). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2010]. Available from: http://clinicaltrials. gov/ct2/show/NCT00345176. NLM Identifier: NCT00345176. 2010.Google Scholar
  68. 68.
    Frank RN. Growth factors in age-related macular degeneration: pathogenic and therapeutic implications. Ophthalmic Res 1997; 29:341–353.PubMedCrossRefGoogle Scholar
  69. 69.
    Giuffre G. Main posterior watershed zone of the choroid. Variations of its position in normal subjects. Doc Ophthalmol 1989; 72:175–180.PubMedCrossRefGoogle Scholar
  70. 70.
    Straubhaar M, Orgul S, Gugleta K et al. Choroidal laser Doppler flowmetry in healthy subjects. Arch Ophthalmol 2000; 118:211–215.PubMedGoogle Scholar
  71. 71.
    Metelitsina TI, Grunwald JE, Dupont JC et al. Foveolar choroidal circulation and choroidal neovascularization in age-related macular degeneration. Invest Ophthalmol Vis Sci 2008; 49:358–363.PubMedCrossRefGoogle Scholar
  72. 72.
    Starita C, Hussain AA, Pagliarini S et al. Hydrodynamics of ageing Bruch’s membrane: implications for macular disease. Exp Eye Res 1996; 62:565–572.PubMedCrossRefGoogle Scholar
  73. 73.
    Francois J, De Laey JJ, Cambie E et al. Neovascularization after argon laser photocoagulation of macular lesions. Am J Ophthalmol 1975; 79:206–210.PubMedGoogle Scholar
  74. 74.
    Pruett RC, Weiter JJ, Goldstein RB. Myopic cracks, angioid streaks and traumatic tears in Bruch’s membrane. Am J Ophthalmol 1987; 103:537–543.PubMedGoogle Scholar
  75. 75.
    Mullins RF, Olvera MA, Clark AF et al. Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. Exp Eye Res 2007; 84:378–380.PubMedCrossRefGoogle Scholar
  76. 76.
    Stone EM, Braun TA, Russell SR et al. Missense variations in the fibulin 5 gene and age-related macular degeneration. N Engl J Med 2004; 351:346–353.PubMedCrossRefGoogle Scholar
  77. 77.
    Spraul CW, Lang GE, Grossniklaus HE et al. 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 1999; 44 Suppl 1:S10–S32.PubMedCrossRefGoogle Scholar
  78. 78.
    Sheraidah G, Steinmetz R, Maguire J et al. Correlation between lipids extracted from Bruch’s membrane and age. Ophthalmology 1993; 100:47–51.PubMedGoogle Scholar
  79. 79.
    Cherepanoff S, McMenamin P, Gillies MC et al. Bruch’s membrane and choroidal macrophages in early and advanced age-related macular degeneration. Br J Ophthalmol 2010; 94:918–925.PubMedCrossRefGoogle Scholar
  80. 80.
    Steen B, Sejersen S, Berglin L et al. Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes. Invest Ophthalmol Vis Sci 1998; 39:2194–2200.PubMedGoogle Scholar
  81. 81.
    Janssen A, Hoellenriegel J, Fogarasi M et al. Abnormal vessel formation in the choroid of mice lacking tissue inhibitor of metalloprotease-3. Invest Ophthalmol Vis Sci 2008; 49:2812–2822.PubMedCrossRefGoogle Scholar
  82. 82.
    Chen W, Stambolian D, Edwards AO et al. Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci USA 2010; 107:7401–7406.PubMedCrossRefGoogle Scholar
  83. 83.
    Guo L, Hussain AA, Limb GA et al. Age-dependent variation in metalloproteinase activity of isolated human Bruch’s membrane and choroid. Invest Ophthalmol Vis Sci 1999; 40:2676–2682.PubMedGoogle Scholar
  84. 84.
    Pham TQ, Kifley A, Mitchell P et al. Relation of age-related macular degeneration and cognitive impairment in an older population. Gerontology 2006; 52:353–358.PubMedCrossRefGoogle Scholar
  85. 85.
    Wong TY, Klein R, Nieto FJ et al. Is early age-related maculopathy related to cognitive function? The Atherosclerosis Risk in Communities Study. Am J Ophthalmol 2002; 134:828–835.PubMedCrossRefGoogle Scholar
  86. 86.
    Klaver CC, Ott A, Hofman A et al. Is age-related maculopathy associated with Alzheimer’s Disease? The Rotterdam Study. Am J Epidemiol 1999; 150:963–968.PubMedGoogle Scholar
  87. 87.
    Loffler KU, Edward DP, Tso MO. Immunoreactivity against tau, amyloid precursor protein and beta-amyloid in the human retina. Invest Ophthalmol Vis Sci 1995; 36:24–31.PubMedGoogle Scholar
  88. 88.
    Luibl V, Isas JM, Kayed R et al. Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest 2006; 116:378–385.PubMedCrossRefGoogle Scholar
  89. 89.
    Isas JM, Luibl V, Johnson LV et al. Soluble and mature amyloid fibrils in drusen deposits. Invest Ophthalmol Vis Sci 2010; 51:1304–1310.PubMedCrossRefGoogle Scholar
  90. 90.
    Dentchev T, Milam AH, Lee VM et al. Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis 2003; 9:184–190.PubMedGoogle Scholar
  91. 91.
    Wang J, Ohno-Matsui K, Yoshida T et al. Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia: Another mechanism of complement activation in age-related macular degeneration. J Cell Physiol 2009; 220:119–128.PubMedCrossRefGoogle Scholar
  92. 92.
    Anderson DH, Talaga KC, Rivest AJ et al. Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res 2004; 78:243–256.PubMedCrossRefGoogle Scholar
  93. 93.
    Shin TM, Isas JM, Hsieh CL et al. Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin. Mol Neurodegener 2008; 3:16.PubMedCrossRefGoogle Scholar
  94. 94.
    Johnson LV, Leitner WP, Rivest AJ et al. The Alzheimer’s A beta-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA 2002; 99:11830–11835.PubMedCrossRefGoogle Scholar
  95. 95.
    Friedman DA, Lukiw WJ, Hill JM. Apolipoprotein E epsilon4 offers protection against age-related macular degeneration. Med Hypotheses 2007; 68:1047–1055.PubMedCrossRefGoogle Scholar
  96. 96.
    Klaver CC, Kliffen M, van Duijn CM et al. Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet 1998; 63:200–206.PubMedCrossRefGoogle Scholar
  97. 97.
    Bainbridge JW, Smith AJ, Barker SS et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 2008; 358:2231–2239.PubMedCrossRefGoogle Scholar
  98. 98.
    Ding JD, Lin J, Mace BE et al. Targeting age-related macular degeneration with Alzheimer’s disease based immunotherapies: anti-amyloid-beta antibody attenuates pathologies in an age-related macular degeneration mouse model. Vision Res 2008; 48:339–345.PubMedCrossRefGoogle Scholar
  99. 99.
    Landa G, Butovsky O, Shoshani J et al. Weekly vaccination with Copaxone (glatiramer acetate) as a potential therapy for dry age-related macular degeneration. Curr Eye Res 2008; 33:1011–1013.PubMedCrossRefGoogle Scholar
  100. 100.
    Guo L, Duggan J, Cordeiro MF. Alzheimer’s disease and retinal neurodegeneration. Curr Alzheimer Res 2010; 7:3–14.PubMedCrossRefGoogle Scholar
  101. 101.
    Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV et al. Identification of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage 2010.Google Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Sam Khandhadia
    • 1
  • Jocelyn Cherry
    • 1
  • Andrew John Lotery
    • 1
  1. 1.Department of Clinical NeurosciencesSouthampton General HospitalSouthamptonUK

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