Literatur

bei betagten, jedoch nicht bei jungen Tieren verursachen kann [159, 160].

Fazit

▬Altersabhängige Veränderungen in der Neuroretina und dem RPE gehen mit einer zunehmenden Anfälligkeit einher, eine AMD zu entwickeln.

▬Zu den altersabhängigen Veränderungen gehören der Verlust des Fundusreflexes, stärkere Sichtbarkeit großer choroidaler Gefäße, Gebiete mit Hypound Hyperpigmentierung, eine merkliche Zunahme der Fundusautofluoreszenz und das Erscheinen fokaler Sub-RPE-Ablagerun- gen, sog. Drusen.

▬Die retinale Alterung ist ein multifaktorieller Prozess, der sowohl umweltbedingte Schäden als auch genetische Prädisposition mit einschließt.

▬Unter den altersabhängigen Veränderungen auf zellulärer Ebene haben der Verlust an mitochondrialer Funktion, erhöhte ROS-Produktion, Anhäufung oxidativer Schäden, Akkumulation von Lipofuszin, eine veränderte Immunantwort und Veränderungen der Bruch-Membran eine Schlüsselfunktion inne.

▬Oxidative Schäden spielen offenbar eine zentrale Rolle bei der retinalen Alterung und können möglicherweise durch den Einsatz systemischer Antioxidanzien günstig beeinflusst werden.

Literatur

[1]Harman D (1981) The aging process. Proc Natl Acad Sci U S A 78(11): 7124–8

[2]Margrain TH, Boulton ME (2005) Sensory impairment. In: Johnson M (ed) The Cambridge Handbook of Age and Aging. University Press, Cambridge, p 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, p 125–151

[4]Zarbin MA (2004) Current concepts in the pathogenesis of agerelated macular degeneration. Arch Ophthalmol 122(4): 598–614

[5]de Jong PT (2006) Age-related macular degeneration. N Engl J Med 355(14): 1474–85

[6]Bengtson VL, Putney NM, Johnson ML (2005) In: Johnson M (ed) The Cambridge Handbook of Age and Aging. University Press, Cambridge, p 3–20

[7]Carnes BA, Staats DO, Sonntag WE (2008) Does senescence give rise to disease? Mech Ageing Dev 129(12): 693–9

[8]Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3): 298–300

[9]Boulton ME (2008) Aging of the retinal pigment epithelium. In: Tombran-Tink J, Barnstable CJC (eds) Visual Transduction and Non-Visual Light Perception. Humana Press, p 403–420

[10]Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc20(4): 145–7

[11]Miquel J, et al. (1980) Mitochondrial role in cell aging. Exp Gerontol 15(6): 575–91

[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: 644–51

[14]Nordgaard CL, et al. (2008) Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration. Invest Ophthalmol Vis Sci 49(7): 2848–55

[15]Kenney MC, et al. (2010) Characterization of Retinal and Blood

3Mitochondrial DNA from Age-related Macular Degeneration Patients. Invest Ophthalmol Vis Sci [epub ahead of print]

[16]Kanski J (2003) Clinical Ophthalmology: A Systematic Approach. Heinemann, Butterworth

[17]Salvi SM, Akhtar S, Currie Z (2006) Ageing changes in the eye. Postgrad Med J 82(971): 581–7

[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): 203–13

[19]Langrova H, et al. (2008) Age-related changes in retinal functional topography. Invest Ophthalmol Vis Sci 49(11): 5024–32

[20]Mohidin N, Yap MK, Jacobs RJ (1999) Influence of age on the multifocal electroretinography. Ophthalmic Physiol Opt 19(6): 481–8

[21]Tzekov RT, Gerth C, Werner JS (2004) Senescence of human multifocal electroretinogram components: a localized approach. Graefes Arch Clin Exp Ophthalmol 242(7): 549–60

[22]Bonnel S, Mohand-Said S, Sahel JA (2003) The aging of the retina. Exp Gerontol 38(8): 825–31

[23]Birch DG, Anderson JL (1992), Standardized full-field electroretinography. Normal values and their variation with age. Arch Ophthalmol 110(11): 1571–6

[24]Jackson GR, Owsley C (2000) Scotopic sensitivity during adulthood. Vision Res 40(18): 2467–73

[25]Owsley C, et al. (2000) Psychophysical evidence for rod vulnerability in age-related macular degeneration. Invest Ophthalmol Vis Sci 41(1): 267–73

[26]Danias J, et al. (2003) Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia glaucomatous mice: comparison with RGC loss in aging C57/BL6 mice. Invest Ophthalmol Vis Sci 44(12): 5151–62

[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): 521–8

[28]Eliasieh K, Liets LC, Chalupa LM (2007) Cellular reorganization in the human retina during normal aging. Invest Ophthalmol Vis Sci 48(6): 2824–30

[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): 1448–52

[31]Cavallotti C, et al. (2004) Age-related changes in the human retina. Can J Ophthalmol 39(1): 61–8

[32]Feuer WJ, et al. (2010) Topographic Differences in the Agerelated Changes in the Retinal Nerve Fiber Layer of Normal Eyes Measured by Stratus Optical Coherence Tomography. J Glaucoma [epub ahead of print]

[33]Gao H, Hollyfield JG (1992) Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 33(1): 1–17

[34]Curcio CA, et al. (1993) Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci 34(12): 3278–96

[35]Leveillard T, et al. (2004) Identification and characterization of rod-derived cone viability factor. Nat Genet 36(7): 755–9

[36]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

[37]Fridlich R, et al. (2009) The thioredoxin-like protein rod-derived cone viability factor (RdCVFL) interacts with TAU and inhibits its phosphorylation in the retina. Mol Cell Proteomics 8(6): 1206–18

[38]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): 293–8

[39]Liets LC, et al. (2006) Dendrites of rod bipolar cells sprout in normal aging retina. Proc Natl Acad Sci U S A 103(32): 12156–60

[40]Terzibasi E, et al. (2009) Age-dependent remodelling of retinal circuitry. Neurobiol Aging 30(5): 819–28

[41]Chen M, et al. (2010) Immune activation in Retinal Aging: A Gene Expression Study. Invest Ophthalmol Vis Sci [epub ahead of print]

[42]Chan-Ling T, et al. (2007) Inflammation and breakdown of the blood-retinal barrier during »physiological aging« in the rat retina: a model for CNS aging. Microcirculation 14(1): 63–76

[43]Xu H, Chen M, Forrester JV (2009) Para-inflammation in the aging retina. Prog Retin Eye Res 28(5): 348–68

[44]Marmor F, Wolfensberger TJ (1998) The Retinal Pigment Epithelium. Oxford University Press, New York Oxford

[45]Hogan MJ, Alvarado JA, Weddell JE (1971) Histology of the Human Eye. Saunders, Philadelphia

[46]Boulton M, Dayhaw-Barker P (2001) The role of the retinal pigment epithelium: topographical variation and ageing changes. Eye15(Pt 3): 384–9

[47]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): 973–84

[48]Streeten BW (1969) Development of the human retinal pigment epithelium and the posterior segment. Arch Ophthalmol 81(3): 383–94

[49]Marshall J (1987) The ageing retina: physiology or pathology? Eye1: 282–295

[50]Burke JM, BS McKay, GJ (1991) Jaffe Retinal pigment epithelial cells of the posterior pole have fewer Na/K adenosine triphosphatase pumps than peripheral cells. Invest Ophthalmol Vis Sci 32(7): 2042–6

[51]Burke JM, Twining SS (1988) Regional comparisons of cathepsin D activity in bovine retinal pigment epithelium. Invest Ophthalmol Vis Sci 29(12): 1789–93

[52]Cabral L, et al. (1990) Regional distribution of lysosomal enzymes in the canine retinal pigment epithelium. Invest Ophthalmol Vis Sci 31(4): 670–6

[53]Panda-Jonas S, Jonas JB, Jakobczyk-Zmija M (1996) Retinal pigment epithelial cell count, distribution, correlations in normal human eyes. Am J Ophthalmol 121(2): 181–9

[54]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): 3312–8

[55]Dorey CK, et al. (1989) Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci 30(8): 1691–9

[56]Feeney-Burns L, Hilderbrand ES, Eldridge S (1984) Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci 25(2): 195–200

[57]Burke JM Hjelmeland LM (2005) Mosaicism of the retinal pigment epithelium: seeing the small picture. Mol Interv 5(4): 241–9

Literatur

[58]Boulton M, et al. (2004) The photoreactivity of ocular lipofuscin. Photochem Photobiol Sci 3(8): 759–64

[59]Boulton ME (2009) Lipofuscin of the retinal pigment epithelium, in Fundus Autofluorescence, N. Lois and J.V. Forrester, Editors. Wolters Kluwer/Lipincott Williams & Wilkins, Philadelphia, p 14–26

[60]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, p 421–462

[61]Ng KP, et al. (2008) Retinal pigment epithelium lipofuscin proteomics. Mol Cell Proteomics 7(7): 1397–405

[62]Sparrow JR Boulton M (2005) RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res 80(5): 595–606

[63]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

[64]Boulton M, et al. (1990) Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium. Vision Res 30(9): 1291–303

[65]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

[66]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): 364–8

[67]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): 18825–30

[68]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): 1107–12

[69]Gaillard ER, et al. (1995) Photophysical studies on human retinal lipofuscin. Photochem Photobiol 61(5): 448–53

[70]Rozanowska M, et al. (2004) Age-related changes in the photoreactivity of retinal lipofuscin granules: role of chloroforminsoluble components. Invest Ophthalmol Vis Sci 45(4): 1052–60

[71]Davies S, et al. (2001) Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells. Free Radic Biol Med 31(2): 256–65

[72]Shamsi FA, Boulton M (2001) Inhibition of RPE lysosomal and antioxidant activity by the age pigment lipofuscin. Invest Ophthalmol Vis Sci 42(12): 3041–6

[73]Godley BF, et al. (2005) Blue light induces mitochondrial DNA damage and free radical production in epithelial cells. J Biol Chem 280(22): 21061–6

[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): 2303–8

[75]Sparrow JR Cai B (2001) Blue light-induced apoptosis of A2Econtaining RPE: involvement of caspase-3 and protection by Bcl-2. Invest Ophthalmol Vis Sci 42(6): 1356–62

[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): 1981–9

[77]Pawlak A, et al. (2003) Comparison of the aerobic photoreactivity of A2E with its precursor retinal. Photochem Photobiol 77(3): 253–8

[78]Rozanowska M, Sarna T (2005) Light-induced damage to the retina: role of rhodopsin chromophore revisited. Photochem Photobiol 81(6): 1305–30

[79]Ben-Shabat S, et al. (2002) Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, evidence of singlet oxygen involvement. Angew Chem Int Ed Engl 41(5): 814–7

[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 U S A 103(44): 16182–7

[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): 562–4

[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): 737–43

[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): 772–80

[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): 24770–80

[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 U S A 99(6): 3842–7

[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. University Press, Oxford p 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): 145–52

[89]Kayatz P, et al. (2001) Oxidation causes melanin fluorescence. Invest Ophthalmol Vis Sci 42(1): 241–6

[90]Sarna T, et al. (2003) Loss of melanin from human RPE with aging: 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): 650–7

[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 Aging 27(7): 983–93

[96]Reeve AK, Krishnan KJ, Turnbull D (2008) Mitochondrial DNA mutations in disease, aging, and neurodegeneration. Ann N Y Acad Sci 1147: 21–9

[97]Jarrett S, AS Lewin, Boulton ME (2010) The importance of mitochondria in age-related and inherited eye disorders. Ophthalmic Res 44: 179–190

[98]Karunadharma PP, et al. (2010) Mitochondrial DNA Damage as a Potential Mechanism for Age-related Macular Degeneration. Invest Ophthalmol Vis Sci [epub ahead of print]

[99]Udar N, et al. (2009) Mitochondrial DNA haplogroups associated with age-related macular degeneration. Invest Ophthalmol Vis Sci 50(6): 2966–74

[100]Barreau E, et al. (1996) Accumulation of mitochondrial DNA deletions in human retina during aging. Invest Ophthalmol Vis Sci37(2): 384–91

[101]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): 815–22

3[102] Nordgaard CL., et al. (2008) Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related

macular degeneration. Invest Ophthalmol Vis Sci 49(7): 2848–2855

[103]Decanini A, et al. (207) Changes in select redox proteins of the retinal pigment epithelium in age-related macular degeneration. Am J Ophthalmol 143(4): 607–15

[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): 4407–20

[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 U S A 103(30): 11282–7

[107]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): 1382–91

[108]Ballinger SW, et al. (1999) Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells. Exp Eye Res 68(6): 765–72

[109]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): 213–23

[110]Schutt F, et al. (2007) Accumulation of A2-E in mitochondrial membranes of cultured RPE cells. Graefes Arch Clin Exp Ophthalmol 245(3): 391–8

[111]Hayasaka S (1989) Aging changes in lipofuscin, lysosomes and melanin in the macular area of human retina and choroid. Jpn J Ophthalmol 33(1): 36–42

[112]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): 125–9

[113]Ogawa T, et al. (2005) Changes in the spatial expression of genes with aging in the mouse RPE/choroid. Mol Vis 11: 380–6

[114]Mizushima N, et al. (2008) Autophagy fights disease through cellular self-digestion. Nature 451(7182): 1069–75

[115]Cuervo AM, et al. (2005) Autophagy and aging: the importance of maintaining »clean« cells. Autophagy 1(3): 131–40

[116]Cuervo AM (2004) Autophagy: many paths to the same end. Mol Cell Biochem 263(1-2): 55–72

[117]Klionsky D, et al. (2007) How shall I eat thee? Autophagy 3(5): 413–6

[118]Sohal RS (1981) Age Pigments. Elsevier/North-Holland Biomedical Press

[119]Terman A, Gustafsson B, Brunk UT (2007) Autophagy, organelles and ageing. J Pathol 211(2): 134–43

[120]Boulton M, et al. (1989) The formation of autofluorescent granules in cultured human RPE. Invest Ophthalmol Vis Sci 30(1): 82–9

[121]Wassell J, et al. (1998) Fluorescence properties of autofluorescent granules generated by cultured human RPE cells. Invest Ophthalmol Vis Sci 39(8): 1487–92

[122]Nilsson SE, et al. (2003) Aging of cultured retinal pigment epithelial cells: oxidative reactions, lipofuscin formation and blue light damage. Doc Ophthalmol 106(1): 13–6

[123]Burke JM, Skumatz CM (1998) Autofluorescent inclusions in long-term postconfluent cultures of retinal pigment epithelium. Invest Ophthalmol Vis Sci 39(8): 1478–86

[124]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): 465–71

[125]Haralampus-Grynaviski NM, et al. (2003) Spectroscopic and morphological studies of human retinal lipofuscin granules. Proc Natl Acad Sci U S A 100(6): 3179–84

[126]Kiffin R, Bandyopadhyay U, Cuervo AM (2006) Oxidative stress and autophagy. Antioxid Redox Signal 8(1–2): 152–62

[127]Kurz T, Terman A, Brunk UT (2007) Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron. Arch Biochem Biophys 462(2): 220–30

[128]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

[129]Winkler BS, et al. (1999) Oxidative damage and age-related macular degeneration. Mol Vis 5: 32

[130]Beatty S, et al. (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45(2): 115–34

[131]Halliwell B, Gutteridge JM (2007) Free Radicals in Biology and Medicine. 3rd ed. Oxford University Press, New York

[132]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): 1417–36

[133]Barker FM, 2nd (2010) Dietary supplementation: effects on visual performance and occurrence of AMD and cataracts. Curr Med Res Opin 26(8): 2011–23

[134]Liles MR, Newsome DA, Oliver PD (1991) Antioxidant enzymes in the aging human retinal pigment epithelium. Arch Ophthalmol 109(9): 1285–8

[135]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): 1562–5

[136]Friedrichson T, et al. (1995) Vitamin E in macular and peripheral tissues of the human eye. Curr Eye Res 14(8): 693–701

[137]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

[138]Beatty S, et al. (2001) Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 42(2): 439–46

[139]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 aging. Biochemistry 44(2): 480–9

[140]Liao JH, Lee JS, Chiou SH (2002) C-terminal lysine truncation increases thermostability and enhances chaperone-like function of porcine alphaB-crystallin. Biochem Biophys Res Commun 297(2): 309–16

[141]Organisciak D, et al. (2006) Genetic, age and light mediated effects on crystallin protein expression in the retina. Photochem Photobiol 82(4): 1088–96

Literatur

[142]Jarrett SG, Albon J, Boulton M (2006) The contribution of DNA repair and antioxidants in determining cell type-specific resistance to oxidative stress. Free Radic Res, 40(11): 1155–65

[143]Crawford DR, Davies KJ (1994) Adaptive response and oxidative stress. Environ Health Perspect 102 Suppl 10: 25–8

[144]Booij JC, et al. (2010) The dynamic nature of Bruch’s membrane. Prog Retin Eye Res 29(1): 1–18

[145]Curcio CA, et al. (2009) Aging, age-related macular degeneration, the response-to-retention of apolipoprotein B-containing lipoproteins. Prog Retin Eye Res 28(6): 393–422

[146]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

[147]Hagema, GS, Mullins RF (1999) Molecular composition of drusen as related to substructural phenotype. Molecular Vision 5: 28

[148]Anderson DH, Radeke MJ, Gallo NB et al. (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res 29(2):95–112

[149]Bird AC (1991) Doyne Lecture. Pathogenesis of retinal pigment epithelial detachment in the elderly; the relevance of Bruch’s membrane change. Eye 5: 1–12

[150]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): 241-51

[151]Ugarte M, Hussain AA, Marshall J (2006) An experimental study of the elastic properties of the human Bruch‘s membranechoroid complex: relevance to ageing. Br J Ophthalmol 90(5): 621–6

[152]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): 775–9

[153]Hewitt AT, Nakazawa K, Newsome DA (1989) Analysis of newly synthesized Bruch‘s membrane proteoglycans. Invest Ophthalmol Vis Sci 30(3): 478–86

[154]Marshall J, et al. (1998) Aging and Bruch’s membrane. In: Marmor MF, Wolfensberger TJ (eds) The Retinal Pigment Epithelium. Oxford University Press, New York Oxford, p 669–692

[155]Friedman DS, et al. (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122(4): 564–72

[156]Martin JE, Sheaff MT (2007) The pathology of ageing: concepts and mechanisms. J Pathol 211(2): 111–3

[157]Curcio CA, Medeiros NE, Millican CL (1996) Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci 37(7): 1236–49

[158]Solbach U, et al. (1997) Imaging of retinal autofluorescence in patients with age-related macular degeneration. Retina 17(5): 385–9

[159]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): 1390–7

[160]Malek G, et al. (2005) Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci U S A 102(33): 11900–5

[161]Bird A, Marshall J (1986) Retinal pigment epithelial detachments in the elderly. Trans Ophthalmol Soc UK 105: 674–682

[162]Archer D (1983) Retinal neovascularization. Trans Ophthalmol Soc UK 103: 2–26

[163]Eagle RC, Jr. (1984) Mechanisms of maculopathy. Ophthalmology 91(6): 613–25