Ageing of the Retina and Retinal Pigment Epithelium

Age-Related Macular Degeneration

Volumn , Issue , 2013, Pages 45-63

  Boulton, M E ^a  

^a UNIVERSITY OF FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84893771325     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-3-642-22107-1_3     Document Type: Chapter

References (162)

1. Harman D (1981) The ageing process. Proc Natl Acad Sci USA 78(11):7124–7128
2. Margrain TH, Boulton ME (2005) Sensory impairment. In: Johnson M (ed) The Cambridge handbook of age and ageing. University Press, Cambridge, pp 121–130
3. Boulton M (1991) Ageing of the retinal pigment epithelium. In: Osborne N, Chader G (eds) Progress in retinal research. Pergamon Press, Oxford, pp 125–151
4. Zarbin MA (2004) Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 122(4): 598–614
5. de Jong PT (2006) Age-related macular degeneration. N Engl J Med 355(14):1474–1485
6. Bengtson VL, Putney NM, Johnson ML (2005) The problem of theory in gerontology today. In: Johnson ML (ed) The Cambridge handbook of age and ageing. Cambridge University Press, Cambridge, pp 3–20
7. Carnes BA, Staats DO, Sonntag WE (2008) Does senescence give rise to disease? Mech Ageing Dev 129(12):693–699
8. Harman D (1956) Ageing: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300
9. Boulton ME (2008) Ageing of the retinal pigment epithelium. In: Tombran-Tink J, Barnstable CJ (eds) Visual transduction and non-visual light perception. Humana Press, Totowa, pp 403–420
10. Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20(4):145–147
11. Miquel J et al (1980) Mitochondrial role in cell ageing. Exp Gerontol 15(6):575–591
12. Jarrett SG et al (2008) Mitochondrial DNA damage and its potential role in retinal degeneration. Prog Retin Eye Res 27(6):596–607
13. Wang AL et al (2008) Increased mitochondrial DNA damage and down-regulation of DNA repair enzymes in aged rodent retinal pigment epithelium and choroid. Mol Vis 14:644–651
14. Nordgaard CL et al (2008) Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of agerelated macular degeneration. Invest Ophthalmol Vis Sci 49(7):2848–2855
15. Kenney MC et al (2010) Characterization of retinal and blood mitochondrial DNA from age-related macular degeneration patients. Invest Ophthalmol Vis Sci 51(8): 4289–4297
16. Kanski J (2003) Clinical ophthalmology: a systematic approach. Butterworth-Heinemann, London
17. Salvi SM, Akhtar S, Currie Z (2006) Ageing changes in the eye. Postgrad Med J 82(971):581–587
18. Guirao A et al (1999) Average optical performance of the human eye as a function of age in a normal population. Invest Ophthalmol Vis Sci 40(1):203–213
19. Langrova H et al (2008) Age-related changes in retinal functional topography. Invest Ophthalmol Vis Sci 49(11): 5024–5032
20. Mohidin N, Yap MK, Jacobs RJ (1999) Influence of age on the multifocal electroretinography. Ophthalmic Physiol Opt 19(6):481–488
21. Tzekov RT, Gerth C, Werner JS (2004) Senescence of human multifocal electroretinogram components: a localized approach. Graefes Arch Clin Exp Ophthalmol 242(7):549–560
22. Bonnel S, Mohand-Said S, Sahel JA (2003) The ageing of the retina. Exp Gerontol 38(8):825–831
23. Birch DG, Anderson JL (1992) Standardized full-field electroretinography. Normal values and their variation with age. Arch Ophthalmol 110(11):1571–1576
24. Jackson GR, Owsley C (2000) Scotopic sensitivity during adulthood. Vision Res 40(18):2467–2473
25. Owsley C et al (2000) Psychophysical evidence for rod vulnerability in age-related macular degeneration. Invest Ophthalmol Vis Sci 41(1):267–273
26. Danias J et al (2003) Quantitative analysis of retinal ganglion cell (RGC) loss in ageing DBA/2NNia glaucomatous mice: comparison with RGC loss in ageing C57/BL6 mice. Invest Ophthalmol Vis Sci 44(12):5151–5162
27. Neufeld AH et al (2002) Loss of retinal ganglion cells following retinal ischemia: the role of inducible nitric oxide synthase. Exp Eye Res 75(5):521–528
28. Eliasieh K, Liets LC, Chalupa LM (2007) Cellular reorganization in the human retina during normal ageing. Invest Ophthalmol Vis Sci 48(6):2824–2830
29. Alamouti B, Funk J (2003) Retinal thickness decreases with age: an OCT study. Br J Ophthalmol 87(7):899–901
30. Eriksson U, Alm A (2009) Macular thickness decreases with age in normal eyes: a study on the macular thickness map protocol in the Stratus OCT. Br J Ophthalmol 93(11):1448–1452
31. Cavallotti C et al (2004) Age-related changes in the human retina. Can J Ophthalmol 39(1):61–68
32. Boulton ME (2009) Lipofuscin of the retinal pigment epithelium. In: Lois N, Forrester JV (eds) Fundus autofluorescence. Wolters Kluwer/Lipincott Williams & Wilkins, Philadelphia, pp 14–26
33. Davies S et al (2001) Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells. Free Radic Biol Med 31(2):256–265
34. Feuer WJ et al (2010) Topographic differences in the agerelated changes in the retinal nervefiber layer of normal eyes measured by Stratus optical coherence tomography. J Glaucoma 20(3):133–138
35. Gao H, Hollyfield JG (1992) Ageing of the human retina. Differential loss of neurons and retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 33(1):1–17
36. Curcio CA et al (1993) Ageing of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci 34(12):3278–3296
37. Leveillard T et al (2004) Identification and characterization of rod-derived cone viability factor. Nat Genet 36(7): 755–759
38. Chalmel F et al (2007) Rod-derived Cone Viability Factor-2 is a novel bifunctional-thioredoxin-like protein with therapeutic potential. BMC Mol Biol 8:74
39. Fridlich R et al (2009) The thioredoxin-like protein rodderived cone viability factor (RdCVFL) interacts with TAU and inhibits its phosphorylation in the retina. Mol Cell Proteomics 8(6):1206–1218
40. Aggarwal P, Nag TC, Wadhwa S (2007) Age-related decrease in rod bipolar cell density of the human retina: an immunohistochemical study. J Biosci 32(2):293–298
41. Liets LC et al (2006) Dendrites of rod bipolar cells sprout in normal ageing retina. Proc Natl Acad Sci USA 103(32): 12156–12160
42. Terzibasi E et al (2009) Age-dependent remodelling of retinal circuitry. Neurobiol Ageing 30(5):819–828
43. Chen M et al (2010) Immune activation in retinal ageing: a gene expression study. Invest Ophthalmol Vis Sci 51(11): 5888–5896
44. Chan-Ling T et al (2007) Inflammation and breakdown of the blood-retinal barrier during “physiological ageing” in the rat retina: a model for CNS ageing. Microcirculation 14(1): 63–76
45. Xu H, Chen M, Forrester JV (2009) Para-inflammation in the ageing retina. Prog Retin Eye Res 28(5):348–368
46. Marmor F, Wolfensberger TJ (1998) The retinal pigment epithelium. Oxford University Press, New York/Oxford
47. Hogan MJ, Alvarado JA, Weddell JE (1971) Histology of the human eye. Saunders, Philadelphia
48. Boulton M, Dayhaw-Barker P (2001) The role of the retinal pigment epithelium: topographical variation and ageing changes. Eye (Lond) 15(Pt 3):384–389
49. Gouras P et al (2010) Topographic and age-related changes of the retinal epithelium and Bruch’s membrane of rhesus monkeys. Graefes Arch Clin Exp Ophthalmol 248(7):973–984
50. Streeten BW (1969) Development of the human retinal pigment epithelium and the posterior segment. Arch Ophthalmol 81(3):383–394
51. Marshall J (1987) The ageing retina: physiology or pathology? Eye (Lond) 1:282–295
52. Burke JM, McKay BS, Jaffe GJ (1991) Retinal pigment epithelial cells of the posterior pole have fewer Na/K adenosine triphosphatase pumps than peripheral cells. Invest Ophthalmol Vis Sci 32(7):2042–2046
53. Burke JM, Twining SS (1988) Regional comparisons of cathepsin D activity in bovine retinal pigment epithelium. Invest Ophthalmol Vis Sci 29(12):1789–1793
54. Cabral L et al (1990) Regional distribution of lysosomal enzymes in the canine retinal pigment epithelium. Invest Ophthalmol Vis Sci 31(4):670–676
55. Panda-Jonas S, Jonas JB, Jakobczyk-Zmija M (1996) Retinal pigment epithelial cell count, distribution, and correlations in normal human eyes. Am J Ophthalmol 121(2):181–189
56. Del Priore LV, Kuo YH, Tezel TH (2002) Age-related changes in human RPE cell density and apoptosis proportion in situ. Invest Ophthalmol Vis Sci 43(10):3312–3318
57. Dorey CK et al (1989) Cell loss in the ageing retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci 30(8):1691–1699
58. Feeney-Burns L, Hilderbrand ES, Eldridge S (1984) Ageing human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci 25(2):195–200
59. Burke JM, Hjelmeland LM (2005) Mosaicism of the retinal pigment epithelium: seeing the small picture. Mol Interv 5(4):241–249
60. Boulton M et al (2004) The photoreactivity of ocular lipofuscin. Photochem Photobiol Sci 3(8):759–764
61. Rozanowska M, Rozanowski B (2008) Visual transduction and age-related changes in lipofuscin. In: Tombran-Tink J, Barnstable CJ (eds) Visual transduction and non-visual light perception. Humana Press, Totowa, pp 421–462
62. Ng KP et al (2008) Retinal pigment epithelium lipofuscin proteomics. Mol Cell Proteomics 7(7):1397–1405
63. Sparrow JR, Boulton M (2005) RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res 80(5):595–606
64. Crouch RK et al. (2010) Human A2E levels are higher in the peripheral (extramacular) RPE than in the macular region of the RPE IOVS. ARVO-E abstract 1300
65. Boulton M et al (1990) Age-related changes in the morphology, absorption andfluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium. Vision Res 30(9): 1291–1303
66. Clancy KMR et al (2000) Atomic force microscopy and near-field scanning optical microscopy measurements of single human retinal lipofuscin granules. J Phys Chem B 104:12098–12101
67. Haralampus-Grynaviski NM et al (2001) Probing the spatial dependence of the emission spectrum of single human retinal lipofuscin granules using near-field scanning optical microscopy. Photochem Photobiol 74(2):364–368
68. Rozanowska M et al (1995) Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species. J Biol Chem 270(32):18825–18830
69. Rozanowska M et al (1998) Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media. Free Radic Biol Med 24(7–8):1107–1112
70. Gaillard ER et al (1995) Photophysical studies on human retinal lipofuscin. Photochem Photobiol 61(5): 448–453
71. Rozanowska M et al (2004) Age-related changes in the photoreactivity of retinal lipofuscin granules: role of chloroform- insoluble components. Invest Ophthalmol Vis Sci 45(4):1052–1060
72. Shamsi FA, Boulton M (2001) Inhibition of RPE lysosomal and antioxidant activity by the age pigment lipofuscin. Invest Ophthalmol Vis Sci 42(12):3041–3046
73. Godley BF et al (2005) Blue light induces mitochondrial DNA damage and free radical production in epithelial cells. J Biol Chem 280(22):21061–21066
74. Schutt F et al (2000) Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci 41(8):2303–2308
75. Sparrow JR, Cai B (2001) Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl-2. Invest Ophthalmol Vis Sci 42(6): 1356–1362
76. Sparrow JR, Nakanishi K, Parish CA (2000) The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci 41(7):1981–1989
77. Pawlak A et al (2003) Comparison of the aerobic photoreactivity of A2E with its precursor retinal. Photochem Photobiol 77(3):253–258
78. Rozanowska M, Sarna T (2005) Light-induced damage to the retina: role of rhodopsin chromophore revisited. Photochem Photobiol 81(6):1305–1330
79. Ben-Shabat S et al (2002) Formation of a nonaoxirane from A2E, a lipofuscinfluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Angew Chem Int Ed Engl 41(5):814–817
80. Zhou J et al (2006) Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci USA 103(44): 16182–16187
81. Bergmann M et al (2004) Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin fluorophore A2-E may contribute to the pathogenesis of agerelated macular degeneration. FASEB J 18(3):562–564
82. Holz FG et al (1999) Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci 40(3):737–743
83. Liu J et al (2008) Restoration of lysosomal pH in RPE cells from cultured human and ABCA4(−/−) mice: pharmacologic approaches and functional recovery. Invest Ophthalmol Vis Sci 49(2):772–780
84. Vives-Bauza C et al (2008) The age lipid A2E and mitochondrial dysfunction synergistically impair phagocytosis by retinal pigment epithelial cells. J Biol Chem 283(36): 24770–24780
85. Finnemann SC, Leung LW, Rodriguez-Boulan E (2002) The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium. Proc Natl Acad Sci USA 99(6):3842–3847
86. Drenos F, Kirkwood TB (2005) Modelling the disposable soma theory of ageing. Mech Ageing Dev 126(1): 99–103
87. Boulton ME (1998) The role of melanin in the RPE. In: Marmor M, Wolfensberger T (eds) The retinal pigment epithelium. Oxford University Press, Oxford, pp 68–85
88. Weiter JJ et al (1986) Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. Invest Ophthalmol Vis Sci 27(2):145–152
89. Kayatz P et al (2001) Oxidation causes melanin fluorescence. Invest Ophthalmol Vis Sci 42(1):241–246
90. Sarna T et al (2003) Loss of melanin from human RPE with ageing: possible role of melanin photooxidation. Exp Eye Res 76(1):89–98
91. Sarna T (1992) Properties and function of the ocular melanin – a photophysical view. J Photochem Photobiol B Biol 12:215–258
92. Zareba M et al (2006) Oxidative stress in ARPE-19 cultures: do melanosomes confer cytoprotection? Free Radic Biol Med 40(1):87–100
93. Rozanowski B et al (2008) The phototoxicity of aged human retinal melanosomes. Photochem Photobiol 84(3): 650–657
94. Feeney L (1978) Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies. Invest Ophthalmol Vis Sci 17(7):583–600
95. Feher J et al (2006) Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Ageing 27(7):983–993
96. Reeve AK, Krishnan KJ, Turnbull D (2008) Mitochondrial DNA mutations in disease, ageing, and neurodegeneration. Ann N Y Acad Sci 1147:21–29
97. Jarrett SG, Boulton ME (2005) Antioxidant up-regulation and increased nuclear DNA protection play key roles in adaptation to oxidative stress in epithelial cells. Free Radic Biol Med 38(10):1382–1391
98. Jarrett S, Lewin AS, Boulton ME (2010) The importance of mitochondria in age-related and inherited eye disorders. Ophthalmic Res 44:179–190
99. Karunadharma PP et al (2010) Mitochondrial DNA damage as a potential mechanism for age-related macular degeneration. Invest Ophthalmol Vis Sci 51(11):5470–5479
100. Udar N et al (2009) Mitochondrial DNA haplogroups associated with age-related macular degeneration. Invest Ophthalmol Vis Sci 50(6):2966–2974
101. Barreau E et al (1996) Accumulation of mitochondrial DNA deletions in human retina during ageing. Invest Ophthalmol Vis Sci 37(2):384–391
102. Nordgaard CL et al (2006) Proteomics of the retinal pigment epithelium reveals altered protein expression at progressive stages of age-related macular degeneration. Invest Ophthalmol Vis Sci 47(3):815–822
103. Decanini A et al (2007) Changes in select redox proteins of the retinal pigment epithelium in age-related macular degeneration. Am J Ophthalmol 143(4):607–615
104. Godley BF et al. (2008) Mitochondrial DNA repair capacity decreases with progression of age-related macular degeneration. Invest Ophthalmol Vis Sci 49: ARVO E-abstract
105. Justilien V et al (2007) SOD2 knockdown mouse model of early AMD. Invest Ophthalmol Vis Sci 48(10):4407–4420
106. Imamura Y et al (2006) Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1- deficient mice: a model of age-related macular degeneration. Proc Natl Acad Sci USA 103(30):11282–11287
107. Ballinger SW et al (1999) Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells. Exp Eye Res 68(6):765–772
108. Jarrett SG, Boulton ME (2007) Poly(ADP-ribose) polymerase offers protection against oxidative and alkylation damage to the nuclear and mitochondrial genomes of the retinal pigment epithelium. Ophthalmic Res 39(4): 213–223
109. Schutt F et al (2007) Accumulation of A2-E in mitochondrial membranes of cultured RPE cells. Graefes Arch Clin Exp Ophthalmol 245(3):391–398
110. Hayasaka S (1989) Ageing changes in lipofuscin, lysosomes and melanin in the macular area of human retina and choroid. Jpn J Ophthalmol 33(1):36–42
111. Boulton M et al (1994) Regional variation and age-related changes of lysosomal enzymes in the human retinal pigment epithelium. Br J Ophthalmol 78(2):125–129
112. Ogawa T et al (2005) Changes in the spatial expression of genes with ageing in the mouse RPE/choroid. Mol Vis 11: 380–386
113. Mizushima N et al (2008) Autophagyfights disease through cellular self-digestion. Nature 451(7182):1069–1075
114. Cuervo AM et al (2005) Autophagy and ageing: the importance of maintaining “clean” cells. Autophagy 1(3):131–140
115. Cuervo AM (2004) Autophagy: many paths to the same end. Mol Cell Biochem 263(1–2):55–72
116. Klionsky DJ et al (2007) How shall I eat thee? Autophagy 3(5):413–416
117. Sohal RS (1981) Age pigments. Elsevier/North-Holland Biomedical Press, Amsterdam
118. Terman A, Gustafsson B, Brunk UT (2007) Autophagy, organelles and ageing. J Pathol 211(2):134–143
119. Boulton M et al (1989) The formation of autofluorescent granules in cultured human RPE. Invest Ophthalmol Vis Sci 30(1):82–89
120. Wassell J et al (1998) Fluorescence properties of autofluorescent granules generated by cultured human RPE cells. Invest Ophthalmol Vis Sci 39(8):1487–1492
121. Nilsson SE et al (2003) Ageing of cultured retinal pigment epithelial cells: oxidative reactions, lipofuscin formation and blue light damage. Doc Ophthalmol 106(1):13–16
122. Burke JM, Skumatz CM (1998) Autofluorescent inclusions in long-term postconfluent cultures of retinal pigment epithelium. Invest Ophthalmol Vis Sci 39(8):1478–1486
123. Krohne TU et al (2010) Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in human retinal pigment epithelial cells. Exp Eye Res 90(3):465–471
124. Haralampus-Grynaviski NM et al (2003) Spectroscopic and morphological studies of human retinal lipofuscin granules. Proc Natl Acad Sci USA 100(6):3179–3184
125. Kiffin R, Bandyopadhyay U, Cuervo AM (2006) Oxidative stress and autophagy. Antioxid Redox Signal 8(1–2):152–162
126. Kurz T, Terman A, Brunk UT (2007) Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron. Arch Biochem Biophys 462(2):220–230
127. Wang AL et al (2009) Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS One 4(1):e4160
128. Winkler BS et al (1999) Oxidative damage and age-related macular degeneration. Mol Vis 5:32
129. Beatty S et al (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45(2):115–134
130. Halliwell B, Gutteridge JM (2007) Free radicals in biology and medicine, 3rd edn. Oxford University Press, New York
131. AREDS (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(10):1417–1436
132. Barker FM 2nd (2010) Dietary supplementation: effects on visual performance and occurrence of AMD and cataracts. Curr Med Res Opin 26(8):2011–2023
133. Liles MR, Newsome DA, Oliver PD (1991) Antioxidant enzymes in the ageing human retinal pigment epithelium. Arch Ophthalmol 109(9):1285–1288
134. Miyamura N et al (2004) Topographic and age-dependent expression of heme oxygenase-1 and catalase in the human retinal pigment epithelium. Invest Ophthalmol Vis Sci 45(5):1562–1565
135. Friedrichson T et al (1995) Vitamin E in macular and peripheral tissues of the human eye. Curr Eye Res 14(8):693–701
136. Castorina C et al (1992) Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age. Neurochem Res 17(6):599–604
137. Beatty S et al (2001) Macular pigment and risk for agerelated macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 42(2): 439–446
138. Maeda A, Crabb JW, Palczewski K (2005) Microsomal glutathione S -transferase 1 in the retinal pigment epithelium: protection against oxidative stress and a potential role in ageing. Biochemistry 44(2):480–489
139. Liao JH, Lee JS, Chiou SH (2002) C-terminal lysine truncation increases thermostability and enhances chaperonelike function of porcine alphaB-crystallin. Biochem Biophys Res Commun 297(2):309–316
140. Organisciak D et al (2006) Genetic, age and light mediated effects on crystallin protein expression in the retina. Photochem Photobiol 82(4):1088–1096
141. Jarrett SG, Albon J, Boulton M (2006) The contribution of DNA repair and antioxidants in determining cell typespecific resistance to oxidative stress. Free Radic Res 40(11):1155–1165
142. Crawford DR, Davies KJ (1994) Adaptive response and oxidative stress. Environ Health Perspect 102(Suppl 10):25–28
143. Booij JC et al (2010) The dynamic nature of Bruch’s membrane. Prog Retin Eye Res 29(1):1–18
144. Curcio CA et al (2009) Ageing, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins. Prog Retin Eye Res 28(6): 393–422
145. Guymer R, Luthert P, Bird A (1999) Changes in Bruch’s membrane and related structures with age. Prog Retin Eye Res 18(1):59–90
146. Hageman GS, Mullins RF (1999) Molecular composition of drusen as related to substructural phenotype. Mol Vis 5:28
147. Anderson DH, Radeke MJ, Gallo NB, Chapin EA, Johnson PT, Curletti CR, Hancox LS, Hu J, Ebright JN, Malek G, Hauser MA, Rickman CB, Bok D, Hageman GS, Johnson LV (2010) The pivotal role of the complement system in ageing and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res 29(2):95–112
148. Bird AC (1991) Doyne Lecture. Pathogenesis of retinal pigment epithelial detachment in the elderly; the relevance of Bruch’s membrane change. Eye (Lond) 5:1–12
149. Chong NH et al (2005) Decreased thickness and integrity of the macular elastic layer of Bruch’s membrane correspond to the distribution of lesions associated with age-related macular degeneration. Am J Pathol 166(1):241–251
150. Ugarte M, Hussain AA, Marshall J (2006) An experimental study of the elastic properties of the human Bruch’s membrane- choroid complex: relevance to ageing. Br J Ophthalmol 90(5):621–626
151. Handa JT et al (1999) Increase in the advanced glycation end product pentosidine in Bruch’s membrane with age. Invest Ophthalmol Vis Sci 40(3):775–779
152. Hewitt AT, Nakazawa K, Newsome DA (1989) Analysis of newly synthesized Bruch’s membrane proteoglycans. Invest Ophthalmol Vis Sci 30(3):478–486
153. Marshall J et al (1998) Ageing and Bruch’s membrane. In: Marmor MF, Wolfensberger TJ (eds) The retinal pigment epithelium. Oxford University Press, New York/Oxford, pp 669–692
154. Friedman DS et al (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122(4):564–572
155. Martin JE, Sheaff MT (2007) The pathology of ageing: concepts and mechanisms. J Pathol 211(2):111–113
156. Curcio CA, Medeiros NE, Millican CL (1996) Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci 37(7):1236–1249
157. Solbach U et al (1997) Imageing of retinal autofluorescence in patients with age-related macular degeneration. Retina 17(5):385–389
158. Ambati J et al (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med 9(11):1390–1397
159. Malek G et al (2005) Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci USA 102(33):11900–11905
160. Bird A, Marshall J (1986) Retinal pigment epithelial detachments in the elderly. Trans Ophthalmol Soc UK 105: 674–682
161. Archer D (1983) Retinal neovascularization. Trans Ophthalmol Soc UK 103:2–26
162. Eagle RC Jr (1984) Mechanisms of maculopathy. Ophthalmology 91(6):613–625