Iron metabolism in the eye: A review

Experimental Eye Research

Volumn 88, Issue 2, 2009, Pages 204-215

  Goralska, M ^a   Ferrell, J ^a   Harned, J ^a   Lall, M ^a   Nagar, S ^a   Fleisher, L N ^a   McGahan, M C ^a  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

Author keywords

ferritin; iron; lens; retina; retinal pigmented epithelium; transferrin

Indexed keywords

ASCORBIC ACID; CERULOPLASMIN; EMOXIPIN; FERRITIN; FERROPORTIN; FLUROTHYL; HEME OXYGENASE 1; HEME OXYGENASE 2; HEPCIDIN; HEPHAESTIN; HYPOXIA INDUCIBLE FACTOR; IRON; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; TEMPOL; THIOCTIC ACID; TRANSFERRIN; TRANSFERRIN RECEPTOR; WNT2 PROTEIN;

ANTIOXIDANT ACTIVITY; AQUEOUS HUMOR; ENZYME LINKED IMMUNOSORBENT ASSAY; EYE; EYE DISEASE; HOMEOSTASIS; HUMAN; IRON METABOLISM; IRON STORAGE; IRON TRANSPORT; LENS; NONHUMAN; PIGMENT EPITHELIUM; PRIORITY JOURNAL; RETINA; REVIEW; ULTRAVIOLET B RADIATION;

ANIMALS; EYE; EYE DISEASES; HOMEOSTASIS; HUMANS; IRON; OXIDATIVE STRESS; SIGNAL TRANSDUCTION;

EID: 62049085406     PISSN: 00144835     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.exer.2008.10.026     Document Type: Review

References (176)

1. Abraham N.G., and Kappas A. Pharmacological and clinical aspects of heme oxygenase. Pharmacol. Rev. 60 (2008) 79-127
2. Acland G.M., Aguirre G.D., Ray J., Zhang Q., Aleman T.S., Cideciyan A.V., Pearce-Kelling S.E., Anand V., Zeng Y., Maguire A.M., Jacobson S.G., Hauswirth W.W., and Bennett J. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28 (2001) 92-95
3. Agarwal V.B., Tiwari S.R., and Ram N. Distribution of calcium, magnesium, iron, copper, zinc and manganese in common mammalian eye lenses. Ind. J. Exp. Biol. 14 (1976) 217-221
4. Alberghini A., Recalcati S., Tacchini L., Santambrogio P., Campanella A., and Cairo G. Loss of the von Hippel Lindau tumor suppressor disrupts iron homeostasis in renal carcinoma cells. J. Biol. Chem. 280 (2005) 3120-3128
5. Alldredge C.D., Schlieve C.R., Miller N.R., and Levin L.A. Pathophysiology of the optic neuropathy associated with Friedreich ataxia. Arch. Ophthalmol. 121 (2003) 1582-1585
6. Arjamaa O., and Nikinmaa M. Oxygen-dependent disease in the retina: role of hypoxia-inducible factors. Exp. Eye Res. 83 (2006) 473-483
7. Aslan M., Cort A., and Yucel I. Oxidative and nitrative stress markers in glaucoma. Free Radic. Biol. Med. 45 (2008) 367-376
8. Bainbridge J.W., Smith A.J., Barker S.S., Robbie S., Henderson R., Balaggan K., Viswanathan A., Holder G.E., Stockman A., Tyler N., Petersen-Jones S., Bhattacharya S.S., Thrasher A.J., Fitzke F.W., Carter B.J., Rubin G.S., Moore A.T., and Ali R.R. Effect of gene therapy on visual function in Leber's congenital amaurosis. N. Engl. J. Med. 358 (2008) 2231-2239
9. Baranano D.E., Rao M., Ferris C.D., and Snyder S.H. Biliverdin reductase: a major physiologic cytoprotectant. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 16093-16098
10. Bavic C.O., Busch C., and Eriksson U. Characterization of a plasma retinol-binding protein membrane receptor expressed in the retinal pigment epithelium. J. Biol. Chem. 267 (1992) 23035-23042
11. Beatty S., Koh H., Phil M., Henson D., and Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 45 (2000) 115-134
12. Beazley K.E., Nurminskaya M., Talbot C.J., and Linsenmayer T.F. Corneal epithelial nuclear ferritin: developmental regulation of ferritin and its nuclear transporter ferritoid. Dev. Dyn. 237 (2008) 2529-2541
13. Bridle K.R., Frazer D.M., Wilkins S.J., Dixon J.L., Purdie D.M., Crawford D.H., Subramaniam V.N., Powell L.W., Anderson G.J., and Ram G.A. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homeostasis. Lancet 361 (2003) 669-673
14. Brooks D.G., Manova-Todorova K., Farmer J., Lobmayr L., Wilson R.B., Eagle Jr. R.C., St. Pierre T.G., and Stambolian D. Ferritin crystal cataracts in hereditary hyperferritinemia cataract syndrome. Investig. Ophthalmol. Vis. Sci. 43 (2002) 1121-1126
15. Bruinink A., Sidler C., and Birchler F. Neurotrophic effects of transferrin on embryonic chick brain and neural retinal cell cultures. Int. J. Dev. Neurosci. 14 (1996) 785-795
16. Cai C., Birk D., and Linsenmayer T. Ferritin is a developmentally regulated nuclear protein of avian corneal epithelial cells. J. Biol. Chem. 272 (1997) 12831-12839
17. Cai C., Ching A., Lagace C., and Linsenmayer T. Nuclear ferritin-mediated protection of corneal epithelial cells from oxidative damage to DNA. Dev. Dyn 237 (2008) 2676-2683
18. Cai C.X., Birk D.E., and Linsenmayer T.F. Nuclear ferritin protects DNA from UV damage in corneal epithelial cells. Mol. Biol. Cell 9 (1998) 1037-1051
19. Cai C.X., and Linsenmayer T.F. Nuclear translocation of ferritin in corneal epithelial cells. J. Cell Sci. 114 (2001) 2327-2334
20. Cellier M., Prive G., Belouchi A., Kwan T., Rodrigues V., Chia W., and Gros P. Nramp defines a family of membrane proteins. Proc. Natl. Acad. Sci. U.S.A. 92 (1995)
21. Chen, H., Liu, B., Lukas, T.J., Suyeoka, G., Wu, G., Neufeld, A.H. Changes in iron-regulatory proteins in the aged rodent neural retina. Neurobiol. Aging, in press., doi:10.1016/j.neurobiolaging.2008.01.002
22. Chen L., Dentchev T., Wong R., Hahn P., Wen R., Bennett J., and Dunaief J.L. Increased expression of ceruloplasmin in the retina following photic injury. Mol. Vis. 9 (2003) 151-158
23. Cheng Q., Gonzalez P., and Zigler Jr. J.S. High level of ferritin light chain mRNA in lens. Biochem. Biophys. Res. Commun. 270 (2000) 349-355
24. Cho S.S., and Hyndman A.G. The ontogeny of transferrin receptors in the embryonic chick retina: an immunohistochemical study. Brain Res. 549 (1991) 327-331
25. Chong T.W., Horwitz L.D., Moore J.W., Sowter H.M., and Harris A.L. A mycobacterial iron chelator, desferri-exochelin, induces hypoxia-inducible factors 1 and 2, NIP3 and vascular endothelial growth factor in cancer cell lines. Cancer Res. 62 (2002) 6924-6927
26. Chowers I., Wong R., Dentchev T., Farkas R.H., Iacovelli J., Gunatilaka T.L., Medeiros N.E., Presley J.B., Campochiaro P.A., Curcio C.A., Dunaief J.L., and Zack D.J. The iron carrier transferrin is upregulated in retinas from patients with age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 47 (2006) 2135-2140
27. Cideciyan A.V., Aleman T.S., Boye S.L., Schwartz S.B., Kaushal S., Roman A.J., Pang J.J., Sumaroka A., Windsor E.A., Wilson J.M., Flotte T.R., Fishman G.A., Heon E., Stone E.M., Byrne B.J., Jacobson S.G., and Hauswirth W.W. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc. Natl. Acad. Sci. U.S.A. (2008) PMID: 18809924 (Sept 22)
28. Corsi B., Cozzi A., Arosio P., Drysdale J., Santambrogio P., Campanella A., Biasiotto G., Albertini A., and Levi S. Human mitochondrial ferritin expressed in HeLa cells incorporatese iron and affects cellular iron metabolism. J. Biol. Chem. 277 (2002) 22430-22437
29. Cozzi A., Corsi B., Levi S., Santambrogio P., Albertini A., and Arosio P. Overexpression of wild type and mutated human ferritin H-chain in HeLa cells: in vivo role of ferritin ferroxidase activity. J. Biol. Chem. 275 (2000) 25122-25129
30. Cozzi A., Levi S., Corsi B., Santambrogio P., Campanella A., Gerardi G., and Arosio P. Role of iron and ferritin in TNFalpha-induced apoptosis in HeLa cells. FEBS Lett. 537 (2003) 187-192
31. Dawczynski J., Blum M., Winnefeld K., and Strobel J. Increased content of zinc and iron in human cataractous lenses. Biol. Trace Elem. Res. 90 (2002) 15-23
32. De Domenico I., Vaughn M.B., Bagley D., Musci G., Ward D.M., and Kaplan J. Ferroportin-medicated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J. 25 (2006) 5396-5404
33. De Domenico I., Ward D.M., di Patti M.C., Jeong S.Y., David S., Musci G., and Kaplan J. Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. EMBO J. 26 (2007) 2823-2831
34. De Domenico I., Ward D.M., Nemeth E., Vaughn M.B., Musci G., Ganz T., and Kaplan J. The molecular basis of ferroportin-linked hemochromatosis. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 8955-8960
35. Dentchev T., Hahn P., and Dunaief J.L. Strong labeling for iron and the iron-handling proteins ferritin and ferroportin in the photoreceptor layer in age-related macular degeneration. Arch. Ophthalmol. 123 (2005) 1745-1746
36. Dernouchamps J.P., Vaerman J.P., Michiels J., and Heremans J.F. La transferrine des liquides endoculaires chez le lapin. Ophthalmologica (Basel) 170 (1975) 72-83
37. Dunaief J.L. Iron induced oxidative damage as a potential factor in age-related macular degeneration: the Cogan Lecture. Investig. Ophthalmol. Vis. Sci. 47 (2006) 4660-4664
38. Dunaief J.L., Richa C., Franks E.P., Schultze R.L., Aleman T.S., Schenck J.F., Zimmerman E.A., and Brooks D.G. Macular degeneration in a patient with aceruloplasminemia, a disease associated with retinal iron overload. Ophthalmology 112 (2005) 1062-1065
39. Eisenstein R.S., Garcia-Mayol D., Pettingell W., and Munro H.N. Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 688-692
40. Elkins J.M., Hewitson K.S., McNeill L.A., Seibel J.F., Schlemminger I., Pugh C.W., Ratcliffe P.J., and Schofield C.J. Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1α. J. Biol. Chem. 278 (2003) 1802-1806
41. Farkas R.H., Chowers I., Hackam A.S., Kageyama M., Nickells R.W., Otteson D.C., Duh E.J., Wang C., Valenta D.R., Gunatilaka T.L., Pease M.E., Quigley H.A., and Zack D.J. Increased expression of iron regulating genes in monkey and human glaucoma. Investig. Ophthalmol. Vis. Sci. 45 (2004) 1410-1417
42. Feng Y., vom Hagen F., Lin J., and Hammes H.-P. Incipient diabetic retinopathy - insights from an experimental model. Ophthalmologica 221 (2007) 269-274
43. Forooghian F., Razavi R., and Timms L. Hypoxia-inducible factor expression in human RPE cells. Br. J. Ophthalmol. 91 (2007) 1406-1410
44. Garland D. Role of site-specific, metal-catalyzed oxidation in lens aging and cataract: a hypothesis. Exp. Eye Res. 50 (1990) 677-682
45. Garner B., Davies M.J., and Truscott R.J. Formation of hydroxyl radicals in the human lens is related to the severity of nuclear cataract. Exp. Eye Res. 70 (2000) 81-88
46. Garner B., Roberg K., Qian M., Brunk U.T., Eaton J.W., and Truscott R.J. Redox availability of lens iron and copper: implications for HO{radical dot} generation in cataract. Redox Rep. 4 (1999) 313-315
47. Garner B., Roberg K., Qian M., Eaton J.W., and Truscott R.J. Distribution of ferritin and redox-active transition metals in normal and cataractous human lenses. Exp. Eye Res. 71 (2000) 599-607
48. Ghosh M.C., Tong W.-H., Zhang D., Ollivierre-Wilson H., Singh A., Krishna M.C., Mitchell J.B., and Rouault T.A. Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IFP2 knockout mice. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 12028-12033
49. Giblin F.J. Glutathione: a vital lens antioxidant. J. Ocul. Pharmacol. Ther. 16 (2000) 121-135
50. Gnana-Prakasam J.P., Martin P.M., Mysona B.A., Roon P., Smith S.B., and Ganapathy V. Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe. Biochem. J. 411 (2008) 79-88
51. Goldenberg-Cohen N., Dadon S., Bat-Chen R.S., Kramer M., Hasanreisoglu M., Eldar I., Weinberger D., and Bahar I. Molecular and histological changes following central retinal artery occlusion in a mouse model. Exp. Eye Res. (2008) 10.1016/j.exer.2008.06.014
52. Goralska M., Dackor R., Holley B.L., and McGahan M.C. Alpha lipoic acid changes Fe uptake and storage in lens epithelial cells. Exp. Eye Res. 76 (2003) 241-248
53. Goralska, M., Fleisher, L.N., McGahan, M.C. Ferritin H- and L-chains in fiber cells from canine and human lenses of different ages. Investig. Ophthalmol. Vis. Sci., in press, doi:10.1167/iovs.08.2230
54. Goralska M., Holley B., and McGahan M.C. The effects of Tempol on ferritin synthesis and Fe metabolism in lens epithelial cells. Biochim. Biophys. Acta 1497 (2000) 51-60
55. Goralska M., Holley B.L., and McGahan M.C. Overexpression of H and L ferritin subunits in lens epithelial cells alters Fe metabolism and cellular response to UVB irradiation. Investig. Ophthalmol. Vis. Sci. 42 (2001) 1721-1727
56. Goralska M., Holley B.L., and McGahan M.C. Identification of a mechanism by which lens epithelial cells limit accumulation of overexpressed H-chain ferritin. J. Biol. Chem. 278 (2003) 42920-42926
57. Goralska, M., Nagar, S., Colitz, C., Fleisher, L.N., McGahan, M.C. Changes in ferritin H- and L-chains in canine lenses with age-related nuclear cataract. Investig. Ophthalmol. Vis. Sci., in press.
58. Goralska M., Nagar S., Fleisher L.N., and McGahan M.C. Differential degradation of ferritin H- and L-chains: accumulation of L-chain-rich ferritin in lens epithelial cells. Investig. Ophthalmol. Vis. Sci. 46 (2005) 3521-3529
59. Gruenheid S., Canonne-Hergaux F., Gauthier S., Hackam D.J., Grinstein S., and Gros P. The iron transport protein NRAMP2 is an integrin membrane glycoprotein that colocalizes with transferrin in the recycling endosomes. J. Exp. Med. 189 (1999) 831-841
60. Gunshin H., Mackenzie B., Berger U.V., Gunshin Y., Romero M.F., Boron W.F., Nussberger S., Gollan J.L., and Hediger M.A. Cloning and characterization of a proton-coupled mammalian metal-ion transporter. Nature 388 (1997) 482-488
61. Guo J.H., Juan S.H., and Aust S.D. Suppression of cell growth by heavy chain ferritin. Biochem. Biophys. Res. Commun. 242 (1998) 39-45
62. Gutteridge J.M.C., Rowley D.A., and Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts. Biochem. J. 199 (1981) 263-265
63. Hadziahmetovic M., Dentchev T., Song Y., Haddad N., He X., Hahn P., Pratico D., Wen R., Harris Z.L., Lambris J., Beard J., and Dunaief J. Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD. Investig. Ophthalmol. Vis. Sci. (2008)
64. Hahn P., Dentchev T., Qian Y., Rouault T., Harris Z.L., and Dunaief J.L. Immunolocalization and regulation of iron handling proteins ferritin and ferroportin in the retina. Mol. Vis. 10 (2004) 598-607
65. Hahn P., Qian Y., Dentchev T., Chen L., Beard J., Harris Z.L., and Dunaief J.L. Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 13850-13855
66. Hahn P., Ying G.S., Beard J., and Dunaief J.L. Iron levels in human retina: sex difference and increase with age. Neuroreport 17 (2006) 1803-1806
67. Hamel C.P., Tsilou E., Pfeffer B.A., Hooks J.J., Detrick B., and Redmond T.M. Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is post-transcriptionally regulated in vitro. J. Biol. Chem. 268 (1993) 15751-15757
68. Harned J., Fleisher L.N., and McGahan M.C. Lens epithelial cells synthesize and secrete ceruloplasmin: effects of ceruloplasmin and transferrin on iron efflux and intracellular iron dynamics. Exp. Eye Res. 83 (2006) 721-727
69. Harned J., Grimes A.M., and McGahan M.C. The effect of UVB irradiation on ferritin subunit synthesis, ferritin assembly and Fe metabolism in cultured canine lens epithelial cells. Photochem. Photobiol. 77 (2003) 440-445
70. Harris Z.L. Aceruloplasminemia. J. Neurol. Sci. 207 (2003) 108-109
71. Harris Z.L., Klomp L.W., and Gitlin J.D. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am. J. Clin. Nutr. 67 (1998) 972S-977S
72. He X., Hahn P., Iacovelli J., Wong R., King C., Bhisitkul R., Massaro-Giordano M., and Dunaief J.L. Iron homeostasis and toxicity in retinal degeneration. Prog. Retin. Eye Res. 26 (2007) 649-673
73. Hewitson K.S., McNeill L.A., Elkins J.M., and Schofield C.J. The role of iron and 2-oxoglutarate oxygenases in signalling. Biochem. Soc. Trans. 31 (2003) 510-515
74. Hunt R.C., and Davis A.A. Release of iron by human retinal pigment epithelial cells. J. Cell Physiol. 152 (1992) 102-110
75. Hyndman A.G., Hockberger P.E., Zeevalk G.D., and Conner J.A. Transferrin can alter physiological properties of retinal neurons. Brain Res. 561 (1991) 318-323
76. Iancu T.C., Rabinowitz H., Brissot P., Guillouzo A., Deugnier Y., and Bourel M. Iron overload in the liver in the baboon. An ultrastructural study. J. Hepatol. 1 (1985) 261-275
77. 2-regulated prolyl hydroxylation. Science 292 (2001) 468-472
78. Johnson M.B., and Enns C.A. Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 104 (2004) 4287-4293
79. Kappas A. A method for interdicting the development of severe jaundice in newborns by inhibiting the production of bilirubin. Pediatrics 113 (2004) 119-123
80. Kim N.D., and Luster A.D. Regulation of immune cells by eicosanoid receptors. Scientific World J. (2007) 1307-1328
81. Kleiman N.J., Wang R.-R., and Spector A. Hydrogen peroxide-induced DNA damage in bovine lens epithelial cells. Mutat. Res. 240 (1990) 35-45
82. Kohgo Y., Yokota M., and Drysdale J.W. Differential turnover of rat liver isoferritins. J. Biol. Chem. 255 (1980) 5195-5200
83. Krishna M.C., Russo A., Mitchell J.B., Goldstein S., Dafni H., and Samuni A. Do nitroxide antioxidants act as scavengers of superoxide or as SOD mimics. J. Biol. Chem. 271 (1996) 26026-26031
84. Krishna M.C., and Samuni A. Nitroxides as antioxidants. Methods Enzymol. 234 (1994) 580-589
85. Kuesap J., Li B., Satarug S., Takeda K., Numata I., Na-Bangchang K., and Shibahara S. Prostaglandin D2 induces heme oxygenase-1 in human retinal pigment epithelial cells. Biochem. Biophys. Res. Commun. 367 (2008) 413-419
86. Lakomaa E.-L., and Eklund P. Trace element analysis of human cataractous lenses by neutron activation analysis and atomic absorption spectrometry with special reference to pseudo-exfoliation of the lens capsule. Ophthamol. Res. 10 (1978) 302-306
87. - activity and glutathione levels in lens epithelial and retinal pigment epithelial cells by its effect on cytosolic aconitase. Investig. Ophthalmol. Vis. Sci. 49 (2008) 310-319
88. Lee P.J., Jiang B.H., Chin B.Y., Iyer N.V., Alam J., Semenza G.J., and Choi A.M.K. Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J. Biol. Chem. 272 (1997) 5375-5381
89. Levi S., Corsi B., Bosisio M., Invernizzi R., Volz A., Sanford D., Arosio P., and Drysdale J. A human mitochondrial ferritin encoded by an intronless gene. J. Biol. Chem. 276 (2001) 24437-24440
90. Levi S., Girelli D., Perrone F., Pasti M., Beaumont C., Corrocher R., Albertini A., and Arosio P. Analysis of ferritins in lymphoblastoid cell lines and in the lens of subjects with hereditary hyperferritinemia-cataract syndrome. Blood 91 (1998) 4180-4187
91. Linsenmayer T., Cai C., Millholland J.M., Beazley K.E., and Fitch J.M. Nuclear ferritin in corneal epithelial cells: tissue-specific nuclear transport and protection from UV-damage. Prog. Retin. Eye Res. 2005 (2005) 139-159
92. Lok C.N., and Ponka P. Identification of a hypoxia response element in the transferrin receptor gene. J. Biol. Chem. 274 (1999) 24147-24152
93. Lou M.F. Redox regulation in the lens. Prog. Retin. Eye Res. 22 (2003) 657-682
94. Ma N., Ding X., Doi M., Izumi N., and Semba R. Cellular and subcellular localization of heme oxygenase-2 in monkey retina. J. Neurocytol. 33 (2004) 407-415
95. +-coupled metal-ion transporters NRAMP1 and DMT1. Pflugers Arch. Eur. J. Physiol. 447 (2004) 571-579
96. MacKenzie E.L., Iwasaki K., and Tsuji Y. Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid. Redox Signalling 10 (2008) 997-1030
97. Maguire A.M., Simonelli F., Pierce E.A., Pugh Jr. E.N., Mingozzi F., Bennicelli J., Banfi S., Marshall K.A., Testa F., Surace E.M., Rossi S., Lyubarsky A., Arruda V.R., Konkle B., Stone E., Sun J., Jacobs J., Dell'Osso L., Hertle R., Ma J.X., Redmond T.M., Zhu X., Hauck B., Zelenaia O., Shindler K.S., Maguire M.G., Wright J.F., Volpe N.J., McDonnell J.W., Auricchio A., High K.A., and Bennett J. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N. Engl. J. Med. 358 (2008) 2240-2248
98. Marlhens F., Bareil C., Griffoin J.M., Zrenner E., Almalric P., Eliaou C., Liu S.Y., Harris E., Redmond T.M., Arnaud B., Claustres M., and Hamel C.P. Mutations in RPE65 cause Leber's congenital amaurosis. Nat. Genet. 17 (1997) 139-141
99. Martin P.M., Gnana-Prakasam J.P., Roon P., Smith R.G., Smith S.B., and Ganapathy V. Expression and polarized localization of the hemochromatosis gene product HFE in retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 47 (2006) 4238-4244
100. 2+ oxidation of a-crystallin produces a 43,000 Da aggregate composed of A and B chains cross-linked by non-reducible covalent bonds. Biochem. Biophys. Res. Commun. 157 (1988) 626-631
101. McGahan M.C. Does the lens serve as a 'sink' for iron during ocular inflammation?. Exp. Eye Res. 54 (1992) 525-530
102. McGahan M.C., Ferrell J.B., Fleisher L.N., Nagar S., Lall M.M., and Harned J. Proteins integral to iron metabolism are regulated by hypoxia-inducible factor-1 in retinal pigmented epithelial cells. Investig. Ophthalmol. Vis. Sci. (2008) Abstract #3970
103. McGahan M.C., and Fleisher L.N. Antioxidant activity of aqueous and vitreous humor from the inflamed rabbit eye. Curr. Eye Res. 5 (1986) 641-645
104. McGahan M.C., and Fleisher L.N. A micromethod for the determination of iron and total iron-binding capacity in intraocular fluids and plasma using electrothermal atomic absorption spectroscopy. Anal. Biochem. 156 (1986) 397-402
105. McGahan M.C., and Fleisher L.N. Inflammation-induced changes in the iron concentration and total iron-binding capacity of the intraocular fluids of rabbits. Graefe's Arch. Clin. Exp. Ophthalmol. 226 (1988) 27-30
106. McGahan M.C., and Fleisher L.N. Cellular response to intravitreal injection of endotoxin and xanthine oxidase in rabbits. Graefe's Arch. Clin. Exp. Ophthalmol. 230 (1992) 463-467
107. McGahan M.C., Grimes A.M., and Fleisher L.N. Transferrin inhibits the ocular inflammatory response. Exp. Eye Res. 58 (1994) 509-511
108. McGahan M.C., Harned J., Goralska M., Sherry B., and Fleisher L.N. Transferrin secretion by lens epithelial cells in culture. Exp. Eye Res. 60 (1995) 667-673
109. McGahan M.C., Harned J., Grimes A.M., and Fleisher L.N. Regulation of ferritin levels in cultured lens epithelial cells. Exp. Eye Res. 59 (1994) 551-556
110. McGahan M.C., Harned J., Mukunnemkeril M., Goralska M., Fleisher L.N., and Ferrell J.B. Iron alters glutamate secretion by regulating cytosolic aconitase activity. Am. J. Physiol. Cell Physiol. 288 (2005) C1117-C1124
111. Merle U., Theilig F., Fein E., Gehrke S., Kallinowski B., Riedel H.D., Bachmann S., Stremmel W., and Kulaksiz H. Localization of the iron-regulatory proteins hemojuvelin and transferrin receptor 2 to the basolateral membrane domain of hepatocytes. Histochem. Cell Biol. 127 (2007) 221-226
112. Millholland J.M., Fitch J.M., Cai C.X., Gibney E.P., Beazley K.E., and Linsenmayer T.F. Ferritoid, a tissue-specific nuclear transport protein for ferritin in corneal epithelial cells. J. Biol. Chem. 278 (2003) 23963-23970
113. Mitchell J.B., Samuni A., Krishna M.C., DeGraff W.G., Ahn M.S., Samuni U., and Russo A. Biologically active metal-independent superoxide dismutase mimics. Biochemistry 29 (1990) 2802-2807
114. Mittag T.W., Hammond B.R., Eakins K.E., and Bhattacherjee P. Ocular responses to superoxide generated by intraocular injection of xanthine oxidase. Exp. Eye Res. 40 (1985) 411-419
115. Moiseyev G., Takahashi Y., Chen Y., Gentleman S., Redmond T.M., Crouch R.K., and Ma J.-X. RPE65 is an iron (II) dependent isomerohydrolase in the retinoid visual cycle. J. Biol. Chem. 281 (2006) 2835-2840
116. Morimura H., Fishman G.A., Grover S.A., Fulton A.B., Berson E.L., and Dryja T.P. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 3088-3093
117. Muckenthaler M., Roy C.N., Custodio A.O., Minana B., deGraaf J., Montross L.K., Andrews N.C., and Hentze M.W. Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat. Genet. 34 (2003) 102-107
118. Muckenthaler M.U., Galy B., and Hentze M.W. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu. Rev. Nutr. 28 (2008) 197-213
119. Mukhopadhyay C.K., Mazumder B., and Fox P.L. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency. J. Biol. Chem. 275 (2000) 21048-21054
120. Nakano A., Cohen M.V., and Downey J.M. Ischemic preconditioning: from basic mechanisms to clinical applications. Pharmacol. Ther. 86 (2000) 263-275
121. Narahari J., Ma R., Wang M., and Walden W.E. The aconitase function of iron regulatory protein 1: genetic studies in yeast implicate its role in iron-mediated redox regulation. J. Biol. Chem. 275 (2000) 16227-16234
122. Nemeth E., and Ganz T. Regulation of iron metabolism by hepcidin. Annu. Rev. Nutr. 26 (2006) 323-342
123. Nemeth E., Tuttle M.S., Powelson J., Vaughn M.B., Donovan A., Ward D.M., Ganz T., and Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306 (2004) 2090-2093
124. Nicolas G., Viatte L., Lou D.Q., Bennoun M., Beaumont C., Kahn A., and Andrews N.C. Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. Nat. Genet. 34 (2003) 97-101
125. Novotny L., Rauko P., and Cojocel C. Alpha-lipoic acid: the potential for use in cancer therapy. Neoplasma 55 (2008) 81-86
126. Obolensky A., B.E., Konijn A.M., Banin E., and Chevion M. Ischemic preconditioning of the rat retina: protective role of ferritin. Free Radic. Biol. Med. 44 (2008) 1286-1294
127. Ohta K., Kikuchi T., Arai S., Yoshida N., Sato A., and Yoshimura N. Protective role of heme oxygenase-1 against endotoxin-induced uveitis in rats. Exp. Eye Res. 77 (2003) 665-673
128. Oksala A. On the occurrence of some trace metals in the eye. Acta Ophthalmol. 32 (1954) 235-244
129. Osaki S., Johnson D.A., and Frieden E. Mobilization of iron from the perfused mammalian liver by a serum copper enzyme, ferroxidase I. J. Biol. Chem. 246 (1971) 3018-3023
130. Packer L., Witt E.H., and Tritschler H.J. Alpha-lipoic acid as a biological antioxidant. Free Radic. Biol. Med. 19 (1995) 227-250
131. Pannen B.H., and Bauer M. Differential regulation of hepatic arterial and portal venous vascular resistance by nitric oxide and carbon monoxide in rats. Life Sci. 62 (1998) 2025-2033
132. Patel B.N., and David S. A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes. J. Biol. Chem. 272 (1997) 20185-20190
133. Patel B.N., Dunn R.J., and David S. Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain. J. Biol. Chem. 275 (2000) 4305-4310
134. Patil K., Bellner L., Gullaro G., Gotlinger K.H., Dunn M.W., and Schwartzman M.L. Heme oxygenase-1 induction attenuates corneal inflammation and accelerates wound healing after epithelial injury. Investig. Ophthalmol. Vis. Sci. 49 (2008) 3379-3386
135. Petersen Shay K., Moreau R.F., Smith E.J., and Hagen T.M. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life 60 (2008) 362-367
136. Picard V., Renaudie F., Porcher C., Hentze M.W., Grandchamp B., and Beaumont C. Overexpression of the ferritin H subunit in cultured erythroid cells changes the intracellular iron distribution. Blood 87 (1996) 2057-2064
137. Privitera M.G., Potenza M., Bucolo C., Leggio G.M., and Drago F. Hemin, an inducer of heme oxygenase-1, lowers intraocular pressure in rabbits. J. Ocul. Pharmacol. Ther. 23 (2007) 232-239
138. Rachmilewitz D., Karmeli F., Okon E., and Samuni A. A novel antiulcerogenic stable radical prevents gastric mucosal lesions in rats. Gut 35 (1994) 1181-1188
139. Redmond T.M., Yu S., Lee E., Bok D., Hamasaki D., Chen N., Goletz P., Ma J.X., Crouch R.K., and Pfeifer K. Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat. Genet. 20 (1998) 344-351
140. Robb A., and Wessling-Resnick M. Regulation of transferrin receptor 2 protein levels by transferrin. Blood 104 (2004) 4294-4299
141. Rolfs A., Kvietikova I., Gassmann M., and Wenger R.H. Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1. J. Biol. Chem. 272 (1997) 20055-20062
142. Rouault T.A. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat. Chem. Biol. 2 (2006) 406-414
143. Rzymkiewicz D.M., Reddan J.R., and Andley U.P. Induction of heme oxygenase-1 modulates cis-aconitase activity in lens epithelial cells. Biochem. Biophys. Res. Commun. 270 (2000) 324-328
144. Salceda S., and Caro J. Hypoxia-inducible factor 1α (HIF-1α) protein is rapidly degraded by the ubiquiting-proteasome system under normoxic conditions: its stabilization by hypoxia depends upon redox-induced changes. J. Biol. Chem. 272 (1997) 22642-22647
145. Salinthone S., Yadav V., Bourdette D.N., and Carr D.W. Lipoic acid: a novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS. Endocr. Metab. Immune Disord. Drug Targets 8 (2008) 132-142
146. Saraswathy S., and Rao N.A. Photoreceptor mitochondrial oxidative stress in experimental autoimmune uveitis. Ophthamol. Res. 40 (2008) 160-164
147. Schaller B., and Graf R. Cerebral ischemic preconditioning: an experimental phenomenon or a clinical important entity of stroke prevention?. J. Neurol. 249 (2002) 1503-1511
148. Schmidt P.J., Toran P.T., Giannetti A.M., Bjorkman P.J., and Andrews N.C. The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression. Cell Metab. 7 (2008) 205-214
149. Scott B.C., Aruoma O.I., Evans P.J., O'Neil C., Ver der Vliet A., Cross C.E., Tritschler H.J., and Halliwell B. Lipoic acid and dihydrolipoic acid as antioxidants. A critical evaluation. Free Radic. Res. 20 (1994) 119-130
150. Sedlak T.W., and Snyder S.H. Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics 113 (2004) 1776-1782
151. Semenza G.J. Targeting HIF-1 for cancer therapy. Nature Rev. Cancer 3 (2003) 721-732
152. Sery T.W., and Petrillo R. Superoxide anion radical as an indirect mediator in ocular inflammatory disease. Curr. Eye Res. 3 (1984) 243-252
153. Shi H., Bencze K.Z., Stemmler T.L., and Philpott C.C. A cytosolic iron chaperone that delivers iron to ferritin. Science 320 (2008) 1207-1210
154. Shoham A., Hadziahmetovic M., Dunaief J.L., Mydlarski M.B., and Schipper H.M. Oxidative stress in diseases of the human cornea. Free Radic. Biol. Med. 45 (2008) 1047-1055
155. Shui Y.B., Arbeit J.M., Johnson R.S., and Beebe D.C. HIF-1: an age-dependent regulator of lens cell proliferation. Investig. Ophthalmol. Vis. Sci. 49 (2008) 4961-4970
156. Siu T.L., Morley J.W., and Coroneo M.T. Toxicology of the retina: advances in understanding the defence mechanisms and pathogenesis of drug- and light-induced retinopathy. Clin. Exp. Ophthalmol. 36 (2008) 176-185
157. Smith A.G., Carthew P., Francis J.E., Edwards R.D., and Dinsdale D. Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload. Hepatology 12 (1990) 1399-1405
158. Sommerschild H.T., and Kirkeboen K.A. Preconditioning-endogenous defence mechanisms of the heart. Acta Anaesthesiol. Scand. 46 (2002) 123-137
159. Spector A. Oxidative stress-induced cataract: mechanism of action. FASEB J. 9 (1995) 1173-1182
160. Spector A. Review: oxidative stress and disease. J. Ocul. Pharmacol. Ther. 16 (2000) 193-201
161. Stocker R., Yamamoto Y., McDonagh A.F., Glazer A.N., and Ames B.N. Bilirubin is an antioxidant of possible physiological importance. Science 235 (1987) 1043-1046
162. Sun M.H., Pang J.H., Chen S.L., Kuo P.C., Chen K.J., Kao L.Y., Wu J.Y., Lin K.K., and Tsao Y.P. Photoreceptor protection against light damage by AAV-mediated overexpression of heme oxygenase-1. Investig. Ophthalmol. Vis. Sci. 49 (2007) 5699-5707
163. Tacchini L., Bianchi L., Bernelli-Zazzera A., and Cairo G. Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation. J. Biol. Chem. 274 (1999) 24142-24146
164. Tauber F.W., and Krause A.C. The role of iron, copper, zinc and manganese in the metabolism of the ocular tissues, with special reference to the lens. Am. J. Ophthalmol. 26 (1943) 260-266
165. Taylor H.R. The biological effects of UV-B on the eye. Photochem. Photobiol. 50 (1989) 489-494
166. Thompson D.A., Gyurus P., Fleischer L.L., Bingham E.L., McHenry C.L., Apfelstedt-Sylla E., Zrenner E., Lorenz B., Richards J.E., Jacobson S.G., Sieving P.A., and Gal A. Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration. Investig. Ophthalmol. Vis. Sci. 41 (2000) 4293-4299
167. Truscott R.J. Age-related nuclear cataract-oxidation is the key. Exp. Eye Res. 80 (2005) 709-725
168. Wang R., Shamloul R., Wang X., Meng Q., and Wu L. Sustained normalization of high blood pressure in spontaneously hypertensive rats by implanted hemin pump. Hypertension 48 (2006) 685-692
169. West S.K., Duncan D., Munoz B., R.G.S., Fred L.P., Bandeen-Roche K., and Schein O.D. Sunlight exposure and risk of lens opacities in a population-based study: the Salisbury Eye Evaluation project. JAMA 280
170. Whitnall M., Rahmanto Y.S., Sutak R., Xu X., Becker E.M., Mikhael M.R., Ponka P., and Richardson D.R. The MCK mouse heart model of Friedreich's ataxia: alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 9757-9762
171. Wu L., and Wang R. Carbon monoxide: endogenous production, physiological functions and pharmacological applications. Pharmacol. Rev. 57 (2005) 585-630
172. Yamaguchi T., Bando M., Nakajima A., Teral M., and Suzuki-Yasumoto M. An application of neutron activation analysis to biological materials. IV. Approach to simultaneous determination of trace elements in human eye tissues with non-destructive neutron activation analysis. J. Radioanal. Chem. 57 (1980) 169-183
173. Yanjun Z., Guangyu L., Bin F., Qing W., Ving J., and Aizhen L. Study of hypoxia-induced expression of IF-1alpha in retinal pigment epithelium. Bull. Exp. Biol. Med. 143 (2007) 323-327
174. Yefimova M.G., Jeanny J.C., Guillonneau X., Keller N., Nguyen-Legros J., Sergeant C., Guillow F., and Courtois Y. Iron, ferritin, transferrin and transferrin receptor in the adult rat retina. Investig. Ophthalmol. Vis. Sci. 41 (2000)
175. Yefimova M.G., Jeanny J.C., Keller N., Sergeant C., Guillonneau X., Beaumont C., and Courtois Y. Impaired retinal iron homeostasis associated with defective phagocytosis in Royal College of Surgeons rats. Investig. Ophthalmol. Vis. Sci. 43 (2002) 537-545
176. Zhu Y., Zhang Y., Ojwang B.A., Brantley M.A.J., and Gidday J.M. Long-term tolerance to retinal ischemia by repetitive hypoxic preconditioning: role of HIF-1 alpha and heme oxygenase-1. Investig. Ophthalmol. Vis. Sci. 48 (2007) 1735-1743