Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD)

Biogerontology

Volumn 14, Issue 5, 2013, Pages 461-482

  Tokarz, Paulina ^a   Kaarniranta, Kai ^b,c   Blasiak, Janusz ^a  

^a UNIVERSITY OF LODZ   (Poland)

^b UNIVERSITY OF EASTERN FINLAND   (Finland)

^c KUOPIO UNIVERSITY HOSPITAL   (Finland)

Author keywords

AMD; Antioxidant enzymes; Oxidative stress; Retinal pigment epithelium; ROS; Small molecular weight antioxidants

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; ASCORBIC ACID; CAROTENOID; CATALASE; COPPER; DNA; DOCOSAHEXAENOIC ACID; ENZYME; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; MANGANESE; MICRORNA; NUCLEIC ACID; PHOTOSENSITIZING AGENT; PIGMENT; POLYUNSATURATED FATTY ACID; REACTIVE OXYGEN METABOLITE; RETINOL; SELENIUM; SUPEROXIDE DISMUTASE; TRANSCRIPTION FACTOR; XANTHOPHYLL; ZEAXANTHIN; ZINC;

ANEMIA; BLUE LIGHT; COPPER DEFICIENCY; DEGENERATIVE DISEASE; DISEASE COURSE; DNA REPAIR; GENETIC VARIABILITY; HUMAN; HYPERBARIC OXYGEN; INFLAMMATION; IRRADIATION; MOLECULAR WEIGHT; NONHUMAN; OXIDATIVE STRESS; OXYGEN CONSUMPTION; PHOTORECEPTOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; RADIATION EXPOSURE; RETINA MACULA AGE RELATED DEGENERATION; REVIEW; ULTRAVIOLET RADIATION;

ANTIOXIDANTS; CATALASE; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; HUMANS; MACULAR DEGENERATION; MOLECULAR WEIGHT; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; SUPEROXIDE DISMUTASE;

EID: 84886925646     PISSN: 13895729     EISSN: 15736768     Source Type: Journal    
DOI: 10.1007/s10522-013-9463-2     Document Type: Review

References (218)

1. Agency for Toxic Substances and Disease Registry (ATSDR) (2005) CERCLA priority list of hazardous substances. Available at: http://www.atsdr.cdc.gov/ cxcx3.html. Accessed 10 Aug 2013
2. Age-Related Eye Disease Study 2 Research Group (2013) Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the age-related eye disease study 2 (AREDS2) randomized clinical trial. JAMA 309:2005-2015
3. Age-Related Eye Disease Study Research 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 119:1417-1436
4. Amstad P, Peskin A, Shah G, Mirault ME, Moret R, Zbinden I, Cerutti P (1991) The balance between Cu, Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. Biochemistry 30:9305-9313
5. Anderson SM, Krinsky NI (1973) Protective action of carotenoid pigments against photodynamic damage to liposomes. Photochem Photobiol 18:403-408
6. Anderson RE, Benolken RM, Dudley PA, Landis DJ, Wheeler TG (1974) Proceedings: polyunsaturated fatty acids of photoreceptor membranes. Exp Eye Res 18:205-213
7. Anderson DH, Mullins RF, Hageman GS, Johnson LV (2002) A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 13:411-431
8. Anderson DH, Talaga KC, Rivest AJ, Barron E, Hageman GS, Johnson LV (2004) Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res 78:243-256
9. Arstila AU, Smith MA, Trump BF (1972) Microsomal lipid peroxidation: morphological characterization. Science 175:530-533
10. Ballinger SW, Van Houten B, Jin GF, Conklin CA, Godley BF (1999) Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells. Exp Eye Res 68:765-772
11. Bannon DI, Abounader R, Lees PS, Bressler JP (2003) Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am J Physiol Cell Physiol 284:C44-C50
12. Beatty S, Boulton M, Henson D, Koh HH, Murray IJ (1999) Macular pigment and age related macular degeneration. Br J Ophthalmol 83:867-877
13. Beatty S, Koh H, Phil M, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45:115-134
14. Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME (2001) Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 42:439-446
15. Beatty S, Chakravarthy U, Nolan JM, Muldrew KA, Woodside JV, Denny F, Stevenson MR (2013) Secondary outcomes in a clinical trial of carotenoids with coantioxidants versus placebo in early age-related macular degeneration. Ophthalmology 120:600-606
16. Behndig A (2008) Corneal endothelial integrity in aging mice lacking superoxide dismutase-1 and/or superoxide dismutase-3. Mol Vis 14:2025-2030
17. Bergeron-Sawitzke J, Gold B, Olsh A, Schlotterbeck S, Lemon K, Visvanathan K, Allikmets R, Dean M (2009) Multilocus analysis of age-related macular degeneration. Eur J Hum Genet 17:1190-1199
18. Bernstein PS, Ahmed F, Liu A, Allman S, Sheng X, Sharifzadeh M, Ermakov I, Gellermann W (2012) Macular pigment imaging in AREDS2 participants: an ancillary study of AREDS2 subjects enrolled at the Moran Eye Center. Invest Ophthalmol Vis Sci 53:6178-6186
19. Bhutto I, Lutty G (2012) Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. Mol Aspects Med 33:295-317
20. Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, de Jong PT, Klaver CC, Klein BE, Klein R (1995) International classification and grading system for age-related maculopathy and age-related degeneration. Surv Ophthalmol 39:367-374
21. Blasiak J, Glowacki S, Kauppinen A, Kaarniranta K (2013) Mitochondrial and nuclear DNA damage and repair in age-related macular degeneration. Int J Mol Sci 14:2996-3010
22. Bloch CA, Ausubel FM (1986) Paraquat-mediated selection for mutations in the manganese-superoxide dismutase gene sodA. J Bacteriol 168:795-798
23. Bone RA, Landrum JT, Tarsis SL (1985) Preliminary identification of the human macular pigment. Vision Res 25:1531-1535
24. Bone RA, Landrum JT, Fernandez L, Tarsis SL (1988) Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Ophthalmol Vis Sci 29:843-849
25. Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, Vidal I, Wang W (1997) Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res 64:211-218
26. Boulton M (1998) The role of melanin in the RPE. In: Marmor MF, Wolfensberger TJ (eds) The retinal pigment epithelium. Oxford University Press, Oxford, pp 68-85
27. Bush RA, Reme CE, Malnoe A (1991) Light damage in the rat retina: the effect of dietary deprivation of N-3 fatty acids on acute structural alterations. Exp Eye Res 53:741-752
28. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP (2000) Oxidative damage and protection of the RPE. Prog Retin Eye Res 19:205-221
29. Chalam KV, Khetpal V, Rusovici R, Balaiya S (2011) A review: role of ultraviolet radiation in age-related macular degeneration. Eye Contact Lens 37:225-232
30. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527-605
31. Chen H, Lukas TJ, Du N, Suyeoka G, Neufeld AH (2009a) Dysfunction of the retinal pigment epithelium with age: increased iron decreases phagocytosis and lysosomal activity. Invest Ophthalmol Vis Sci 50:1895-1902
32. Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, Johnson JA (2009b) Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: critical role for the astrocyte. Proc Natl Acad Sci USA 106:2933-2938
33. Chiba Y, Shimada A, Kumagai N, Yoshikawa K, Ishii S, Furukawa A, Takei S, Sakura M, Kawamura N, Hosokawa M (2009) The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model. Neurochem Res 34:679-687
34. Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH (2008) Dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis. Arch Ophthalmol 126:826-833
35. Chorny M, Hood E, Levy RJ, Muzykantov VR (2010) Endothelial delivery of antioxidant enzymes loaded into non-polymeric magnetic nanoparticles. J Control Release 146:144-151
36. Christen WG, Glynn RJ, Sesso HD, Kurth T, Macfadyen J, Bubes V, Buring JE, Manson JE, Gaziano JM (2012) Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 119:1642-1649
37. Chu Y, Iida S, Lund DD, Weiss RM, DiBona GF, Watanabe Y, Faraci FM, Heistad DD (2003) Gene transfer of extracellular superoxide dismutase reduces arterial pressure in spontaneously hypertensive rats: role of heparin-binding domain. Circ Res 92:461-468
38. Cohen SM, Olin KL, Feuer WJ, Hjelmeland L, Keen CL, Morse LS (1994) Low glutathione reductase and peroxidase activity in age-related macular degeneration. Br J Ophthalmol 78:791-794
39. Cui H, Kong Y, Zhang H (2012) Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct 2012:646354
40. De La Paz M, Anderson RE (1992) Region and age-dependent variation in susceptibility of the human retina to lipid peroxidation. Invest Ophthalmol Vis Sci 33:3497-3499
41. De La Paz MA, Zhang J, Fridovich I (1996) Antioxidant enzymes of the human retina: effect of age on enzyme activity of macula and periphery. Curr Eye Res 15:273-278
42. 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 43:3312-3318
43. Delcourt C, Cristol JP, Léger CL, Descomps B, Papoz L (1999) Associations of antioxidant enzymes with cataract and age-related macular degeneration. The POLA study. Pathologies Oculaires Liées à l'Age. Ophthalmology 106:215-222
44. Delcourt C, Carriere I, Delage M, Barberger-Gateau P, Schalch W (2006) Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age-related maculopathy and cataract: the POLA study. Invest Ophthalmol Vis Sci 47:2329-2335
45. Deleon E, Lederman M, Berenstein E, Meir T, Chevion M, Chowers I (2009) Alteration in iron metabolism during retinal degeneration in rd10 mouse. Invest Ophthalmol Vis Sci 50:1360-1365
46. Delori FC, Goger DG, Dorey CK (2001) Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Invest Ophthalmol Vis Sci 42:1855-1866
47. Desler C, Marcker ML, Singh KK, Rasmussen LJ (2011) The importance of mitochondrial DNA in aging and cancer. J Aging Res 2011:407536
48. Dong X, Li Z, Wang W, Zhang W, Liu S, Zhang X (2011) Protective effect of canolol from oxidative stress-induced cell damage in ARPE-19 cells via an ERK mediated antioxidative pathway. Mol Vis 17:2040-2048
49. Dorey CK, Wu G, Ebenstein D, Garsd A, Weiter JJ (1989) Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci 30:1691-1699
50. Dunaief JL, Dentchev T, Ying GS, Milam AH (2002) The role of apoptosis in age-related macular degeneration. Arch Ophthalmol 120:1435-1442
51. Edge R, McGarvey DJ, Truscott TG (1997) The carotenoids as anti-oxidants - a review. J Photochem Photobiol B 41:189-200
52. Elroy-Stein O, Bernstein Y, Groner Y (1986) Overproduction of human Cu/Zn-superoxide dismutase in transfected cells: extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation. EMBO J 5:615-622
53. Erie JC, Good JA, Butz JA, Pulido JS (2009) Reduced zinc and copper in the retinal pigment epithelium and choroid in age-related macular degeneration. Am J Ophthalmol 147:276-282
54. Esfandiary H, Chakravarthy U, Patterson C, Young I, Hughes AE (2005) Association study of detoxification genes in age related macular degeneration. Br J Ophthalmol 89:470-474
55. Eye Disease Case-Control Study Group (1993) Antioxidant status and neovascular age-related macular degeneration. Arch Ophthalmol 111:104-109
56. Farnsworth CC, Stone WL, Dratz EA (1979) Effects of vitamin E and selenium deficiency on the fatty acid composition of rat retinal tissues. Biochim Biophys Acta 552:281-293
57. Feeney-Burns L, Hilderbrand ES, Eldridge S (1984) Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci 25:195-200
58. Feng Z, Liu Z, Li X, Jia H, Sun L, Tian C, Jia L, Liu J (2010) α-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J Nutr Biochem 21:1222-1231
59. Fine SL, Berger JW, Maguire MG, Ho AC (2000) Age-related macular degeneration. New Engl J Med 342:483-492
60. Foote CS, Denny RW (1968) Chemistry of singet oxygen. VII Quenching by -carotene. J Am Chem Soc 90:6233-6235
61. Frank RN (1997) Growth factors in age-related macular degeneration: pathogenic and therapeutic implications. Ophthalmic Res 29:341-353
62. Frank RN, Amin RH, Puklin JE (1999) Antioxidant enzymes in the macular retinal pigment epithelium of eyes with neovascular age-related macular degeneration. Am J Ophthalmol 127:694-709
63. Friedrichson T, Kalbach HL, Buck P, van Kuijk FJ (1995) Vitamin E in macular and peripheral tissues of the human eye. Curr Eye Res 14:693-701
64. Girijashanker K, He L, Soleimani M, Reed JM, Li H, Liu Z, Wang B, Dalton TP, Nebert DW (2008) Slc39a14 gene encodes ZIP14, a metal/bicarbonatesymporter: similarities to the ZIP8 transporter. Mol Pharmacol 73:1413-1423
65. Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MO (1988) Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol 128:700-710
66. Gotoh N, Yamada R, Matsuda F, Yoshimura N, Iida T (2008) Manganese superoxide dismutase gene (SOD2) polymorphism and exudative age-related macular degeneration in the Japanese population. Am J Ophthalmol 146:146-147
67. Haegerstrom-Portnoy G (1988) Short-wavelength-sensitive-cone sensitivity loss with aging: a protective role for macular pigment? J Opt Soc Am A 5:2140-2144
68. Halliwell B, Gutteridge JM (1985) The importance of free radicals and catalytic metal ions in human diseases. Mol Aspects Med 8:89-193
69. Ham WT Jr, Ruffolo JJ Jr, Mueller HA, Clarke AM, Moon ME (1978) Histologic analysis of photochemical lesions produced in rhesus retina by short-wave-length light. Invest Ophthalmol Vis Sci 17:1029-1035
70. Haque R, Chun E, Howell JC, Sengupta T, Chen D, Kim H (2012) MicroRNA-30b-mediated regulation of catalase expression in human ARPE-19 cells. PLoS ONE 7:e42542
71. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298-300
72. Hayes KC (1978) Retinal degeneration in monkeys induced by deficiencies of vitamin E or A. Invest Ophthalmol Vis Sci 13:499-510
73. He L, Girijashanker K, Dalton TP, Reed J, Li H, Soleimani M, Nebert DW (2006) ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family: characterization of transporter properties. Mol Pharmacol 70:171-180
74. He Y, Ge J, Burke JM, Myers RL, Dong ZZ, Tombran-Tink J (2010) Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress. J Ocul Biol Dis Inform 3:92-108
75. Hinton DR, He S, Lopez PF (1998) Apoptosis in surgically excised choroidal neovascular membranes in age-related macular degeneration. Arch Ophthalmol 116:203-209
76. Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L, Ufret RL, Salomon RG, Perez VL (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med 14:194-198
77. Holz FG, Schutt F, Kopitz J, Eldred GE, Kruse FE, Volcker HE, Cantz M (1999) Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci 40:737-743
78. Hunter JJ, Morgan JI, Merigan WH, Sliney DH, Sparrow JR, Williams DR (2012) The susceptibility of the retina to photochemical damage from visible light. Prog Retin Eye Res 31:28-42
79. Izumi-Nagai K, Nagai N, Ohgami K, Satofuka S, Ozawa Y, Tsubota K, Umezawa K, Ohno S, Oike Y, Ishida S (2007) Macular pigment lutein is antiinflammatory in preventing choroidal neovascularisation. Arterioscler Thromb Vasc Biol 27:2555-2562
80. Jain A, Lamark T, Sjøttem E, Larsen KB, Awuh JA, Øvervatn A, McMahon M, Hayes JD, Johansen T (2010) p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 285:22576-22591
81. Jia L, Liu Z, Sun L, Miller SS, Ames BN, Cotman CW, Liu J (2007) Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid. Invest Ophthalmol Vis Sci 48:339-348
82. Jia L, Dong Y, Yang H, Pan X, Fan R, Zhai L (2011) Serum superoxide dismutase and malondialdehyde levels in a group of Chinese patients with age-related macular degeneration. Aging Clin Exp Res 23:264-267
83. Jiang C, Ganther H, Lu J (2000) Monomethyl selenium-specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. Mol Carcinog 29:236-250
84. Jin GF, Hurst JS, Godley BF (2001) Rod outer segments mediate mitochondrial DNA damage and apoptosis in human retinal pigment epithelium. Curr Eye Res 23:11-19
85. Johnson LV, Ozaki S, Staples MK, Erickson PA, Anderson DH (2000) A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res 70:441-449
86. Jorgensen K, Skibsted LH (1993) Carotenoid scavenging of radicals. Effect of carotenoid structure and oxygen partial pressure on antioxidative activity. Z Lebensm Unters Forsch 196:423-429
87. Julien S, Biesemeier A, Kokkinou D, Eibl O, Schraermeyer U (2011) Zinc deficiency leads to lipofuscin accumulation in the retinal pigment epithelium of pigmented rats. PLoS ONE 6:e29245
88. Jünemann AG, Stopa P, Michalke B, Chaudhri A, Reulbach U, Huchzermeyer C, Schlötzer-Schrehardt U, Kruse FE, Zrenner E, Rejdak R (2013) Levels of aqueous humor trace elements in patients with non-exsudative age-related macular degeneration: a case-control study. PLoS ONE 8:e56734
89. Junghans A, Sies H, Stahl W (2001) Macular pigments lutein and zeaxanthin as blue light filters studied in liposomes. Arch Biochem Biophys 391:160-164
90. Justilien V, Pang JJ, Renganathan K, Zhan X, Crabb JW, Kim SR, Sparrow JR, Hauswirth WW, Lewin AS (2007) SOD2 knockdown mouse model of early AMD. Invest Ophthalmol Vis Sci 48:4407-4420
91. Kaarniranta K, Salminen A, Haapasalo A, Soininen H, Hiltunen M (2011) Age-related macular degeneration (AMD): Alzheimer's disease in the eye? J Alzheimers Dis 24:615-631
92. Kaarniranta K, Sinha D, Blasiak J, Kauppinen A, Veréb Z, Salminen A, Boulton ME, Petrovski G (2013) Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration. Autophagy 9(7):973-984
93. Kamei M, Yoneda K, Kume N, Suzuki M, Itabe H, Matsuda K, Shimaoka T, Minami M, Yonehara S, Kita T, Kinoshita S (2007) Scavenger receptors for oxidised lipoprotein in age-related macular degeneration. Invest Ophthalmol Vis Sci 48:1801-1807
94. Kaneko H, Dridi S, Tarallo V, Gelfand BD, Fowler BJ, Cho WG, Kleinman ME, Ponicsan SL, Hauswirth WW, Chiodo VA, Karikó K, Yoo JW, Lee DK, Hadziahmetovic M, Song Y, Misra S, Chaudhuri G, Buaas FW, Braun RE, Hinton DR, Zhang Q, Grossniklaus HE, Provis JM, Madigan MC, Milam AH, Justice NL, Albuquerque RJ, Blandford AD, Bogdanovich S, Hirano Y, Witta J, Fuchs E, Littman DR, Ambati BK, Rudin CM, Chong MM, Provost P, Kugel JF, Goodrich JA, Dunaief JL, Baffi JZ, Ambati J (2011) DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 471:325-330
95. Khavinson VKh, Lezhava TA, Monaselidze JR, Jokhadze TA, Dvalishvili NA, Bablishvili NK, Trofimova SV (2003) Peptide Epitalon activates chromatin at the old age. Neuro Endocrinol Lett 24:329-333
96. Kijlstra A, La Heij EC, Hendrikse F (2005) Immunological factors in the pathogenesis and treatment of age-related macular degeneration. Ocul Immunol Inflamm 13:3-11
97. Kijlstra A, Tian Y, Kelly ER, Berendschot TT (2012) Lutein: more than just a filter for blue light. Prog Retin Eye Res 31:303-315
98. 2 in NF-kappa B activation. Free Radic Biol Med 45:885-896
99. Kimura K, Isashiki Y, Sonoda S, Kakiuchi-Matsumoto T, Ohba N (2000) Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. Am J Ophthalmol 130:769-773
100. Klein LR, MacLeish PR, Wiesel TN (1990) Immunolabelling by a newt retinal pigment epithelium antibody during retinal development and regeneration. J Comp Neurol 293:331-339
101. Klein BE, Howard KP, Lee KE, Iyengar SK, Sivakumaran TA, Klein R (2012) The relationship of cataract and cataract extraction to age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 119:1628-1633
102. Kliment CR, Suliman HB, Tobolewski JM, Reynolds CM, Day BJ, Zhu X, McTiernan CF, McGaffin KR, Piantadosi CA, Oury TD (2009) Extracellular superoxide dismutase regulates cardiac function and fibrosis. J Mol Cell Cardiol 47:730-742
103. Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S, Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Kobayashi A, Yamamoto M, Yue Z, Uchiyama Y, Kominami E, Tanaka K (2007) Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131:1149-1163
104. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, Kim M, Nishito Y, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 12:213-223
105. Kondo N, Bessho H, Honda S, Negi A (2009) SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Mol Vis 15:1819-1826
106. Kowalski M, Bielecka-Kowalska A, Oszajca K, Eusebio M, Jaworski P, Bartkowiak J, Szemraj J (2010) Manganese superoxide dismutase (MnSOD) gene (Ala-9Val, Ile58Thr) polymorphism in patients with age-related macular degeneration (AMD). Med Sci Monit 16:CR190-CR196
107. Kowluru RA, Zhong Q (2011) Beyond AREDS: is there a place for antioxidant therapy in the prevention/treatment of eye disease? Invest Ophthalmol Vis Sci 52:8665-8671
108. Kretzscharm M, Muller D (1993) Aging, training and exercise. A review of effects on plasma glutathione and lipid peroxides. Sports Med 10:196-209
109. Krinsky NI, Deneke SM (1982) Interaction of oxygen and oxy-radicals with carotenoids. J Natl Cancer Inst 69:205-210
110. Kritchevsky SB, Bush AJ, Pahor M, Gross MD (2000) Serum carotenoids and markers of inflammation in nonsmokers. Am J Epidemiol 152:1065-1071
111. Krohne TU, Stratmann NK, Kopitz J, Holz FG (2010) Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in human retinal pigment epithelial cells. Exp Eye Res 90:465-471
112. Kutty RK, Samuel W, Jaworski C, Duncan T, Nagineni CN, Raghavachari N, Wiggert B, Redmond TM (2010) MicroRNA expression in human retinal pigment epithelial (ARPE-19) cells: increased expression of microRNA-9 by N-(4-hydroxyphenyl) retinamide. Mol Vis 16:1475-1486
113. Kuusisto E, Salminen A, Alafuzoff I (2001) Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies. NeuroReport 12:2085-2090
114. Kuusisto E, Salminen A, Alafuzoff I (2002) Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation. Neuropathol Appl Neurobiol 28:228-237
115. Lam S, Tso MO, Gurne DH (1990) Amelioration of retinal photic injury in albino rats by dimethylthiourea. Arch Ophthalmol 108:1751-1757
116. Landrum JT, Bone RA (2001) Lutein, zeaxanthin, and macular pigment. Arch Biochem Biophys 385:28-40
117. Lang CA, Naryshkin S, Schneider DL, Mills BJ, Lindeman R (1992) Low blood glutathione levels in healthy aging adults. J Lab Clin Med 120:720-725
118. Lau A, Wang XJ, Zhao F, Villeneuve NF, Wu T, Jiang T, Sun Z, White E, Zhang DD (2010) A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol Cell Biol 30:3275-3285
119. Lee JM, Calkins MJ, Chan K, Kan YW, Johnson JA (2003a) Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 278:12029-12038
120. Lee JM, Shih AY, Murphy TH, Johnson JA (2003b) NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem 278:37948-37956
121. Lee TB, Moon YS, Choi CH (2012) Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin-resistant AML subline. Cell Biol Toxicol 28:11-18
122. Lee YS, Cheon IS, Kim BH, Kwon MJ, Lee HW, Kim TY (2013) Loss of extracellular superoxide dismutase induces severe IL-23-mediated skin inflammation in mice. J Invest Dermatol 133:732-741
123. Liles MR, Newsome DA, Oliver PD (1991) Antioxidant enzymes in the aging human retinal pigment epithelium. Arch Ophthalmol 109:1285-1288
124. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, Shokat KM, Lavail MM, Walter P (2007) IRE1 signaling affects cell fate during the unfolded protein response. Science 318:944-949
125. Lin H, Qian J, Castillo AC, Long B, Keyes KT, Chen G, Ye Y (2011) Effect of miR-23 on oxidant-induced injury in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 52:6308-6314
126. Liu Z, Sun L, Zhu L, Jia X, Li X, Jia H, Wang Y, Weber P, Long J, Liu J (2007) Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction. J Neurochem 103:2690-2700
127. Lopez PF, Grossniklaus HE, Lambert HM, Aaberg TM, Capone A Jr, Sternberg P Jr, L'Hernault N (1991) Pathologic features of surgically excised subretinal neovascular membranes in age-related macular degeneration. Am J Ophthalmol 112:647-656
128. Lu L, Hackett SF, Mincey A, Lai H, Campochiaro PA (2006) Effects of different types of oxidative stress in RPE cells. J Cell Physiol 206:119-125
129. Lu L, Oveson BC, Jo YJ, Lauer TW, Usui S, Komeima K, Xie B, Campochiaro PA (2009) Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage. Antioxid Redox Signal 11:715-724
130. Luhmann UF, Robbie S, Munro PM, Barker SE, Duran Y, Luong V, Fitzke FW, Bainbridge JW, Ali RR, MacLaren RE (2009) The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages. Invest Ophthalmol Vis Sci 50:5934-5943
131. Macular Degeneration Association (2013) Available at http:// maculardegenerationassociation.org/
132. Majji AB, Cao J, Chang KY, Hayashi A, Aggarwal S, Grebe RR, De Juan E (2000) Age-related retinal pigment epithelium and Bruch's membrane degeneration in senescence-accelerated mouse. Invest Ophthalmol Vis Sci 41:3936-3942
133. Maksimenko AV, Vavaev AV (2012) Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. Enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress. Heart Int 7:e3
134. Maksimenko AV, Golubykh VL, Tischenko EG (2004) The combination of modified antioxidant enzymes for anti-thrombotic protection of the vascular wall: the significance of covalent connection of superoxide dismutase and catalase activities. J Pharm Pharmacol 56:1463-1468
135. Mares-Perlman JA, Brady WE, Klein R, Klein BE, Bowen P, Stacewicz-Sapuntzakis M, Palta M (1995) Serum antioxidants and age-related macular degeneration in a population-based case-control study. Arch Ophthalmol 113:1518-1523
136. Martin P, Fareh M, Poggi MC, Boulukos KE, Pognonec P (2006) Manganese is highly effective in protecting cells from cadmium intoxication. Biochem Biophys Res Commun 351:294-299
137. McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049-6055
138. Miceli MV, Liles MR, Newsome DA (1994) Evaluation of oxidative processes in human pigment epithelial cells associated with retinal outer segment phagocytosis. Exp Cell Res 214:242-249
139. Min JY, Lim SO, Jung G (2010) Downregulation of catalase by reactive oxygen species via hypermethylation of CpG island II on the catalase promoter. FEBS Lett 584:2427-2432
140. Miyamura N, Ogawa T, Boylan S, Morse LS, Handa JT, Hjelmeland LM (2004) Topographic and age-dependent expression of heme oxygenase-1 and catalase in the human retinal pigment epithelium. Invest Ophthalmol Vis Sci 45:1562-1565
141. 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 14:835-846
142. Nagaoka U, Kim K, Jana NR, Doi H, Maruyama M, Mitsui K, Oyama F, Nukina N (2004) Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions. J Neurochem 91:57-68
143. National Eye Institute (2013) Available at http://www.nei.nih.gov/. Accessed 10 Aug 2013
144. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E (1988) Oral zinc in macular degeneration. Arch Ophthalmol 106:192-198
145. Nicolas MG, Fujiki K, Murayama K, Suzuki MT, Shindo N, Hotta Y, Iwata F, Fujimura T, Yoshikawa Y, Cho F, Kanai A (1996) Studies on the mechanism of early onset macular degeneration in cynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress. Exp Eye Res 62:399-408
146. Ohira A, Tanito M, Kaidzu S, Kondo T (2003) Glutathione peroxidase induced in rat retinas to counteract photic injury. Invest Ophthalmol Vis Sci 44:1230-1236
147. Organisciak DT, Winkler BS (1994) Retinal light damage: practical and theoretical considerations. Prog Retin Eye Res 13:1-29
148. Organisciak DT, Wang HM, Li ZY, Tso MO (1985) The protective effect of ascorbate in retinal light damage of rats. Invest Ophthalmol Vis Sci 26:1580-1588
149. Organisciak DT, Jiang YL, Wang HM, Bicknell I (1990) The protective effect of ascorbic acid in retinal light damage of rats exposed to intermittent light. Invest Ophthalmol Vis Sci 31:1195-1202
150. Organisciak DT, Xie A, Wang HM, Jiang YL, Darrow RM, Donoso LA (1991) Adaptive-changes in visual cell transduction protein-levels-effect of light. Exp Eye Res 53:773-779
151. Organisciak DT, Bicknell IR, Darrow RM (1992) The effects of l-and d-ascorbic acid administration on retinal tissue levels and light damage in rats. Curr Eye Res 11:231-241
152. Organisciak DT, Darrow RM, Jiang YL, Blanks JC (1996) Retinal light damage in rats with altered levels of rod outer segment docosahexaenoate. Invest Ophthalmol Vis Sci 37:2243-2257
153. Organisciak DT, Darrow RM, Barsalou L, Darrow RA, Kutty RK, Kutty G, Wiggert B (1998) Light history and age-related changes in retinal light damage. Invest Ophthalmol Vis Sci 39:1107-1116
154. Packer L (1993) Antioxidant action of carotenoids in vitro and in vivo and protection against oxidation of human low-density lipoproteins. Ann NY Acad Sci 691:48-60
155. Pease PL, Adams AJ, Nuccio E (1987) Optical density of human macular pigment. Vision Res 27:705-710
156. Penfold PL, Killingsworth MC, Sarks SH (1985) Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol 223:69-76
157. Quan X, Lim SO, Jung G (2011) Reactive oxygen species downregulate catalase expression via methylation of a CpG island in the Oct-1 promoter. FEBS Lett 585:3436-3441
158. Ragsdale SW (2009) Nickel-based enzyme systems. J Biol Chem 284:18571-18575
159. Ramkumar HL, Zhang J, Chan CC (2010) Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD). Prog Retin Eye Res 29:169-190
160. Ramkumar HL, Tuo J, de Shen F, Zhang J, Cao X, Chew EY, Chan CC (2013) Nutrient supplementation with n3 polyunsaturated fatty acids, lutein, and zeaxanthin decrease A2E accumulation and VEGF expression in the retinas of Ccl2/Cx3cr1-deficient mice on Crb1rd8 background. J Nutr 143:1129-1135
161. Ranchon I, Gorrand JM, Cluzel J, Droy-Lefaix MT, Doly M (1999) Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract. Invest Ophthalmol Vis Sci 40:1191-1199
162. Rapp LM, Williams TP (1979) Damage to the albino rat retina produced by low intensity light. Photochem Photobiol 29:731-733
163. Rapp LM, Williams TP (1980) The role of ocular pigmentation in protecting against retinal light damage. Vision Res 20:1127-1131
164. Recasens JF, Green K (1992) The effects of age and inflammation on antioxidant enzyme activity in the eye. AGE 15:114-117
165. Rex TS, Tsui I, Hahn P, Maguire AM, Duan D, Bennett J, Dunaief JL (2004) Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress. Hum Gene Ther 15:960-967
166. Rozanowska M, Jarvis-Evans J, Korytowski W, Boulton ME, Burke JM, Sarna T (1995) Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species. J Biol Chem 270:18825-18830
167. Ryoo HD, Domingos PM, Kang MJ, Steller H (2007) Unfolded protein response in a Drosophila model for retinal degeneration. EMBO J 26:242-252
168. Ryu E, Fridley BL, Tosakulwong N, Bailey KR, Edwards AO (2010) Genome-wide association analyses of genetic, phenotypic, and environmental risks in the age-related eye disease study. Mol Vis 17:2811-2821
169. Samiec PS, Drews-Botsch C, Flagg E, Kurtz JC, Sternberg P Jr, Reed RL, Jones DP (1998) Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Free Radic Biol Med 24:699-704
170. SanGiovanni JP, Chew EY, Clemons TE, Davis MD, Ferris FL 3rd, Gensler GR, Lindblad AS, Milton RC, Seddon JM, Sperduto RD, Age-Related Eye Disease Study Research Group (2007) The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS Report No. 20. Arch Ophthalmol 125:671-679
171. Satarug S, Kikuchi M, Wisedpanichkij R, Li B, Takeda K, Na-Bangchang K, Moore MR, Hirayama K, Shibahara S (2008) Prevention of cadmium accumulation in retinal pigment epithelium with manganese and zinc. Exp Eye Res 87:587-593
172. Sato M, Bremner I (1993) Oxygen free radicals and metallothionein. Free Radic Biol Med 14:325-337
173. Scott MD, Meshnick SR, Eaton JW (1987) Superoxide dismutase-rich bacteria: paradoxical increase in oxidant toxicity. J Biol Chem 262:3640-3645
174. Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT et al (1994) Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 272:1413-1420
175. Seddon JM, Gensler G, Klein ML, Milton RC (2006) C-reactive protein and homocysteine are associated with dietary and behavioral risk factors for age related macular degeneration. Nutrition 22:441-443
176. Shaban H, Gazzotti P, Richter C (2001) Cytochrome c oxidase inhibition by N-retinyl-N-retinylidene ethanolamine, a compound suspected to cause age-related macula degeneration. Arch Biochem Biophys 394:111-116
177. Shamsi FA, Boulton M (2001) Inhibition of RPE lysosomal and antioxidant activity by the age pigment lipofuscin. Invest Ophthalmol Vis Sci 42:3041-3046
178. Shen XL, Jia JH, Zhao P, Fan R, Pan XY, Yang HM, Liu L (2012) Changes in blood oxidative and antioxidant parameters in a group of Chinese patients with age-related macular degeneration. J Nutr Health Aging 16:201-204
179. Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA, Murphy TH (2003) Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci 23:3394-3406
180. Sies H, Stahl W, Sundquist AR (1992) Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. Ann NY Acad Sci 669:7-20
181. Singh S, Dao D, Srivastava S, Awasthi Y (1984) Purification and characterization of glutathione S-transferases in human retina. Curr Eye Res 3:1273-1280
182. Snellen EL, Verbeek AL, van Den Hoogen GW, Cruysberg JR, Hoyng CB (2002) Neovascular age-related macular degeneration and its relationship to antioxidant intake. Acta Ophthalmol Scand 80:368-371
183. Snodderly DM, Auran JD, Delori FC (1984) The macular pigment. II. Spatial distribution in primate retinas. Invest Ophthalmol Vis Sci 25:674-685
184. Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ (1998) Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol 82:907-910
185. Song D, Song Y, Hadziahmetovic M, Zhong Y, Dunaief JL (2012) Systemic administration of the iron chelator deferiprone protects against light-induced photoreceptor degeneration in the mouse retina. Free Radic Biol Med 53:64-71
186. 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 42:1356-1362
187. Sparrow JR, Nakanishi K, Parish CA (2000) The lipofuscinfluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci 41:1981-1989
188. Sparrow JR, Zhou J, Ben-Shabat S, Vollmer H, Itagaki Y, Nakanishi K (2002) Involvement of oxidative mechanisms in blue-light-induced damage to A2E-laden RPE. Invest Ophthalmol Vis Sci 43:1222-1227
189. Sparrow JR, Zhou J, Cai B (2003) DNA is a target of the photodynamic effects elicited in A2E-laden RPE by blue-light illumination. Invest Ophthalmol Vis Sci 44:2245-2251
190. Sreekumar PG, Spee C, Ryan SJ, Cole SPC, Kannan R, Hinton DR (2012) Mechanism of RPE cell death in α-crystallin deficient mice: a novel and critical role for MRP1-mediated GSH efflux. PLoS ONE 7:e33420
191. Strauss O (2005) The retinal pigment epithelium in visual function. Physiol Rev 85:845-881
192. Synowiec E, Pogorzelska M, Blasiak J, Szaflik J, Szaflik JP (2012) Genetic polymorphism of the iron-regulatory protein-1 and -2 genes in age-related macular degeneration. Mol Biol Rep 39:7077-7087
193. Synowiec E, Sliwinski T, Danisz K, Blasiak J, Sklodowska A, Romaniuk D, Watala C, Szaflik J, Szaflik JP (2013) Association between polymorphism of the NQO1, NOS3 and NFE2L2 genes and AMD. Front Biosci (Landmark Ed) 18:80-90
194. Tanito M, Kaidzu S, Anderson RE (2007) Delayed loss of cone and remaining rod photoreceptor cells due to impairment of choroidal circulation after acute light exposure in rats. Invest Ophthalmol Vis Sci 48:1864-1872
195. Tantin D, Schild-Poulter C, Wang V, Hache RJ, Sharp PA (2005) The octamer binding transcription factor Oct-1 is a stress sensor. Cancer Res 65:10750-10758
196. 2 induce catalase and metallothionein gene expression in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 36:1271-1279
197. Tate DJ Jr, Miceli MV, Newsome DA (1997) Zinc induces catalase expression in cultured fetal human retinal pigment epithelial cells. Curr Eye Res 16:1017-1023
198. Tuo J, Bojanowski CM, Zhou M, Shen D, Ross RJ, Rosenberg KI, Cameron DJ, Yin C, Kowalak JA, Zhuang Z et al (2007) Murine ccl2/cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration. Invest Ophthalmol Vis Sci 48:3827-3836
199. Ueta T, Inoue T, Furukawa T, Tamaki Y, Nakagawa Y, Imai H, Yanagi Y (2012) Glutathione peroxidase 4 is required for maturation of photoreceptor cells. J Biol Chem 287:7675-7682
200. van Herpen-Broekmans WMR, Klopping-Ketelaars IAA, Bots ML, Kluft C, Princen H, Hendriks HFJ, Tijburg LBM, van Poppel G, Kardinaal AFM (2004) Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation. Eur J Epidemiol 19:915-921
201. Vargas MR, Johnson DA, Sirkis DW, Messing A, Johnson JA (2008) Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J Neurosci 28:13574-13581
202. Viiri J, Hyttinen JMT, Ryhänen T, Rilla K, Paimela T, Kuusisto E, Siitonen A, Urtti A, Salminen A, Kaarniranta K (2010) p62/sequestosome 1 as a regulator of proteasome inhibitor-induced autophagy in human retinal pigment epithelial cells. Mol Vision 16:1399-1414
203. Wassell J, Davies S, Bardsley W, Boulton M (1999) The photoreactivity of the retinal age pigment lipofuscin. J Biol Chem 20:23828-23832
204. Wiegand RD, Giusto NM, Rapp LM, Anderson RE (1983) Evidence for rod outer segment lipid peroxidation following constant illumination of the rat retina. Invest Ophthalmol Vis Sci 24:1433-1435
205. Wills NK, Kalariya N, Sadagopa Ramanujam VM, Lewis JR, Haji Abdollahi S, Husain A, van Kuijk FJ (2009) Human retinal cadmium accumulation as a factor in the etiology of age-related macular degeneration. Exp Eye Res 89:79-87
206. Witting LA (1965) Lipid peroxidation in vivo. J Am Oil Chem Soc 42:908-913
207. World Health Organization (2013) Available at http://www.who.int/en/. Accessed 10 Aug 2013
208. Wysokinski D, Danisz K, Blasiak J, Dorecka M, Romaniuk D, Szaflik J, Szaflik JP (2013) An association of transferrin gene polymorphism and serum transferrin levels with age-related macular degeneration. Exp Eye Res 106:14-23
209. Yang LP, Wu LM, Guo XJ, Tso MO (2007) Activation of endoplasmic reticulum stress in degenerating photoreceptors of the rd1 mouse. Invest Ophthalmol Vis Sci 48:5191-5198
210. Yang LP, Wu LM, Guo XJ, Li Y, Tso MO (2008) Endoplasmic reticulum stress is activated in light-induced retinal degeneration. J Neurosci Res 86:910-919
211. Youssef PN, Sheibani N, Albert DM (2011) Retinal light toxicity. Eye (Lond) 25:1-14
212. Yu BP (1994) Cellular defenses against damage from reactive oxygen species. Physiol Rev 74:139-162
213. Yu DY, Cringle SJ (2001) Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease. Prog Retin Eye Res 20:175-208
214. Zadlo A, Rozanowska MB, Burke JM, Sarna TJ (2007) Photobleaching of retinal pigment epithelium melanosomes reduces their ability to inhibit iron-induced peroxidation of lipids. Pigment Cell Res 20:52-60
215. Zatloukal K, Stumptner C, Fuchsbichler A, Heid H, Schnoelzer M, Kenner L, Kleinert R, Prinz M, Aguzzi A, Denk H (2002) p62 is a common component of cytoplasmic inclusions in protein aggregation diseases. Am J Pathol 160:255-263
216. Zhang J, Tuo J, Shen D, Li W, Chan C-C (2013) Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1 deficient mice on Crb1rd8 background. Synapse 67(8):515-531
217. Zhong Y, Li J, Wang JJ, Chen C, Tran JT, Saadi A, Yu Q, Le YZ, Mandal MN, Anderson RE, Zhang SX (2012) X-box binding protein 1 is essential for the anti-oxidant defense and cell survival in the retinal pigment epithelium. PLoS ONE 7:e38616
218. Zhuo P, Goldberg M, Herman L, Lee BS, Wang H, Brown RL, Foster CB, Peters U, Diamond AM (2009) Molecular consequences of genetic variations in the glutathione peroxidase 1 selenoenzyme. Cancer Res 69:8183-8190