Oxidation and age-related macular degeneration: insights from molecular biology

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a multifactorial disease, and current therapy predominantly limits damage only when it has already occurred. The macula is a source of high metabolic activity, and is therefore exposed to correspondingly high levels of reactive oxygen species (ROS). With age, the balance between production of ROS and local antioxidant levels is shifted, and damage ensues. Systemic ROS and antioxidant levels in AMD reflect these local processes. Genetic studies investigating mutations in antioxidant genes in AMD are inconclusive and further studies are indicated, especially to determine the role of mitochondria. Oral antioxidant supplements could be beneficial, and diet modification may help. Future treatments might either increase antioxidant capacity or reduce the production of ROS, using methods such as genetic manipulation. This article reviews the role of oxidative stress in AMD and the potential therapies that might have a role in preventing the blindness resulting from this disease.

[1]  K. Nakashima,et al.  [The Rotterdam study]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.

[2]  F. Ferris,et al.  Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial. , 2010, Investigative ophthalmology & visual science.

[3]  G. Aldini,et al.  Supplementation with lutein or lutein plus green tea extracts does not change oxidative stress in adequately nourished older adults. , 2010, The Journal of nutritional biochemistry.

[4]  Steffen Schmitz-Valckenberg,et al.  Combined confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography imaging of reticular drusen associated with age-related macular degeneration. , 2010, Ophthalmology.

[5]  Ashutosh Kumar,et al.  NF-kappaB inhibitory action of resveratrol: a probable mechanism of neuroprotection in experimental diabetic neuropathy. , 2010, Biochemical and biophysical research communications.

[6]  M. Pinazo-Durán,et al.  Oxidative stress response in the adult rat retina and plasma after repeated administration of methamphetamine , 2010, Neurochemistry International.

[7]  Y. Bardak,et al.  Oxidative Macromolecular Damage in Age-Related Macular Degeneration , 2009, Current eye research.

[8]  M. Grant,et al.  Delivery of antioxidant enzyme genes to protect against ischemia/reperfusion-induced injury to retinal microvasculature. , 2009, Investigative ophthalmology & visual science.

[9]  S. Tsang,et al.  Erythropoetin receptor expression in the human diabetic retina , 2009, BMC Research Notes.

[10]  P. Pelicci,et al.  Impaired expression of p66Shc, a novel regulator of B-cell survival, in chronic lymphocytic leukemia. , 2009, Blood.

[11]  M. Korbonits,et al.  Cannabinoids for clinicians: the rise and fall of the cannabinoid antagonists , 2009, European journal of endocrinology.

[12]  M. Sporn,et al.  Synthetic triterpenoids attenuate cytotoxic retinal injury: cross-talk between Nrf2 and PI3K/AKT signaling through inhibition of the lipid phosphatase PTEN. , 2009, Investigative ophthalmology & visual science.

[13]  T. Rex,et al.  Neuroprotection of photoreceptors by direct delivery of erythropoietin to the retina of the retinal degeneration slow mouse. , 2009, Experimental eye research.

[14]  U. Testa,et al.  Triterpenoids as new promising anticancer drugs. , 2009, Anti-cancer drugs.

[15]  U. Adiguzel,et al.  EFFECTS OF INTRAVITREAL BEVACIZUMAB IN REPEATED DOSES: An Experimental Study , 2009, Retina.

[16]  H. Petty,et al.  Association of superoxide anions with retinal pigment epithelial cell apoptosis induced by mononuclear phagocytes. , 2009, Investigative Ophthalmology and Visual Science.

[17]  F. V. van Kuijk,et al.  Cadmium-induced apoptotic death of human retinal pigment epithelial cells is mediated by MAPK pathway. , 2009, Experimental eye research.

[18]  R. Funk,et al.  The influence of sublethal blue light exposure on human RPE cells , 2009, Molecular vision.

[19]  R. Libby,et al.  Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration. , 2009, American journal of physiology. Cell physiology.

[20]  A. Negi,et al.  SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy , 2009, Molecular vision.

[21]  Anand Swaroop,et al.  Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. , 2009, Annual review of genomics and human genetics.

[22]  Yang Hu,et al.  Anti-inflammatory and antioxidant effects of SERPINA3K in the retina. , 2009, Investigative ophthalmology & visual science.

[23]  F. Lamoke,et al.  Neuroprotective role of erythropoietin by antiapoptosis in the retina , 2009, Journal of neuroscience research.

[24]  J. Haines,et al.  Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria. , 2009, Investigative ophthalmology & visual science.

[25]  Ling Wang,et al.  Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells , 2009, Molecular vision.

[26]  P. Campochiaro,et al.  Oxidative stress promotes ocular neovascularization , 2009, Journal of cellular physiology.

[27]  P. Mitchell,et al.  Mitochondrial DNA Variants of Respiratory Complex I that Uniquely Characterize Haplogroup T2 Are Associated with Increased Risk of Age-Related Macular Degeneration , 2009, PloS one.

[28]  A. Kampik,et al.  Hypoxia/reoxygenation induces CTGF and PAI-1 in cultured human retinal pigment epithelium cells. , 2009, Experimental eye research.

[29]  M. Pangburn,et al.  Oxidative Stress Renders Retinal Pigment Epithelial Cells Susceptible to Complement-mediated Injury* , 2009, The Journal of Biological Chemistry.

[30]  D. Hu,et al.  Erythropoietin protects retinal pigment epithelial cells from oxidative damage. , 2009, Free radical biology & medicine.

[31]  F. Mascarelli,et al.  Amyloid‐β(1‐42) alters structure and function of retinal pigmented epithelial cells , 2009, Aging cell.

[32]  R. McManus,et al.  NF-κB regulation: the nuclear response , 2009, Journal of cellular and molecular medicine.

[33]  Takehiro Michikawa,et al.  Serum antioxidants and age-related macular degeneration among older Japanese. , 2009, Asia Pacific journal of clinical nutrition.

[34]  S. Kim,et al.  Complement activation by bisretinoid constituents of RPE lipofuscin. , 2009, Investigative ophthalmology & visual science.

[35]  C. Rao,et al.  Curcumin protects retinal cells from light-and oxidant stress-induced cell death. , 2009, Free radical biology & medicine.

[36]  P. Campochiaro,et al.  Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage. , 2009, Antioxidants & redox signaling.

[37]  J. Bena,et al.  Assessing Susceptibility to Age-related Macular Degeneration with Proteomic and Genomic Biomarkers* , 2009, Molecular & Cellular Proteomics.

[38]  M. Kantorow,et al.  Mitochondrial function and redox control in the aging eye: role of MsrA and other repair systems in cataract and macular degenerations. , 2009, Experimental eye research.

[39]  A. Kampik,et al.  Subtoxic oxidative stress induces senescence in retinal pigment epithelial cells via TGF-beta release. , 2009, Investigative ophthalmology & visual science.

[40]  C. Glittenberg,et al.  Daytime levels of melatonin in patients with age‐related macular degeneration , 2009, Acta ophthalmologica.

[41]  H. Hara,et al.  Zeaxanthin, a Retinal Carotenoid, Protects Retinal Cells against Oxidative Stress , 2009, Current eye research.

[42]  S. Ennis,et al.  Association between the SERPING1 gene and age-related macular degeneration: a two-stage case–control study , 2008, The Lancet.

[43]  P. D. de Jong,et al.  Sunlight exposure, antioxidants, and age-related macular degeneration. , 2008, Archives of ophthalmology.

[44]  N. Bhaskar,et al.  Possible degradation/biotransformation of lutein in vitro and in vivo: isolation and structural elucidation of lutein metabolites by HPLC and LC-MS (atmospheric pressure chemical ionization). , 2008, Free radical biology & medicine.

[45]  P. Gouras,et al.  Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): effects of age and gender , 2008, Graefe's Archive for Clinical and Experimental Ophthalmology.

[46]  J. L. Ding,et al.  Thioredoxin-like 6 protects retinal cell line from photooxidative damage by upregulating NF-kappaB activity. , 2008, Free radical biology & medicine.

[47]  R. Yamada,et al.  Manganese superoxide dismutase gene (SOD2) polymorphism and exudative age-related macular degeneration in the Japanese population. , 2008, American journal of ophthalmology.

[48]  S. Fisher,et al.  Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA , 2008, Nature Genetics.

[49]  R. Chuck,et al.  Demonstration by redox fluorometry that sulforaphane protects retinal pigment epithelial cells against oxidative stress. , 2008, Investigative ophthalmology & visual science.

[50]  W. Hauswirth,et al.  Downregulation of p22phox in retinal pigment epithelial cells inhibits choroidal neovascularization in mice. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[51]  K. Tsubota,et al.  Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. , 2008, The American journal of pathology.

[52]  S. Davies,et al.  The Phototoxicity of Aged Human Retinal Melanosomes † , 2008, Photochemistry and photobiology.

[53]  S. Priglinger,et al.  The protective effect of quercetin against oxidative stress in the human RPE in vitro. , 2008, Investigative ophthalmology & visual science.

[54]  F. Mascarelli,et al.  Prematurely senescent ARPE-19 cells display features of age-related macular degeneration. , 2008, Free radical biology & medicine.

[55]  R. Klein,et al.  The epidemiology of retinal reticular drusen. , 2008, American journal of ophthalmology.

[56]  Joe G Hollyfield,et al.  Oxidative damage–induced inflammation initiates age-related macular degeneration , 2008, Nature Medicine.

[57]  N. Yoshimura,et al.  Circulating hematopoietic stem cells in patients with neovascular age-related macular degeneration. , 2007, Investigative ophthalmology & visual science.

[58]  P. Campochiaro,et al.  Increased expression of glial cell line‐derived neurotrophic factor protects against oxidative damage‐induced retinal degeneration , 2007, Journal of neurochemistry.

[59]  J. Sangiovanni,et al.  Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: relation with docosahexaenoic acid. , 2007, Investigative ophthalmology & visual science.

[60]  M. Nangaku,et al.  Antioxidative effects of erythropoietin. , 2007, Kidney international. Supplement.

[61]  Gonçalo R. Abecasis,et al.  A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration , 2007, Proceedings of the National Academy of Sciences.

[62]  P. Mitchell,et al.  Mitochondrial DNA haplogroups and age-related maculopathy. , 2007, Archives of ophthalmology.

[63]  F. Muller,et al.  Trends in oxidative aging theories. , 2007, Free radical biology & medicine.

[64]  I. Deary,et al.  Complement C3 variant and the risk of age-related macular degeneration. , 2007, The New England journal of medicine.

[65]  C. Reilly,et al.  Age-related macular degeneration and retinal protein modification by 4-hydroxy-2-nonenal. , 2007, Investigative ophthalmology & visual science.

[66]  A. Lotery,et al.  Progress in defining the molecular biology of age related macular degeneration , 2007, Human Genetics.

[67]  N. Osborne,et al.  Flupirtine attenuates sodium nitroprusside-induced damage to retinal photoreceptors, in situ , 2007, Brain Research Bulletin.

[68]  Y. Tano,et al.  Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration , 2007, Molecular vision.

[69]  T. Wong,et al.  Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis , 2007, BMJ : British Medical Journal.

[70]  D. Hu,et al.  Phototoxicity in Human Retinal Pigment Epithelial Cells Promoted by Hypericin, a Component of St. John’s Wort † , 2007, Photochemistry and photobiology.

[71]  P. Mitchell,et al.  Circulating inflammatory markers and hemostatic factors in age-related maculopathy: a population-based case-control study. , 2007, Investigative ophthalmology & visual science.

[72]  N. Kitteringham,et al.  Extract of Ginkgo biloba induces phase 2 genes through Keap1-Nrf2-ARE signaling pathway. , 2007, Life sciences.

[73]  J. Forrester,et al.  Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments. , 2007, Experimental eye research.

[74]  C. Nordgaard,et al.  Changes in select redox proteins of the retinal pigment epithelium in age-related macular degeneration. , 2007, American journal of ophthalmology.

[75]  B. Brown,et al.  Experimental hypoxia in human eyes: Implications for ischaemic disease , 2007, Clinical Neurophysiology.

[76]  A. Holmgren,et al.  Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in the cardiovascular system. , 2007, American journal of physiology. Heart and circulatory physiology.

[77]  A. Javadzadeh,et al.  Enhanced susceptibility of low-density lipoprotein to oxidation in wet type age-related macular degeneration in male patients. , 2007, Saudi medical journal.

[78]  P. Mitchell,et al.  Elevated serum homocysteine, low serum vitamin B12, folate, and age-related macular degeneration: the Blue Mountains Eye Study. , 2007, American journal of ophthalmology.

[79]  Ning Zhang,et al.  Stimulation of apical and basolateral VEGF-A and VEGF-C secretion by oxidative stress in polarized retinal pigment epithelial cells. , 2006, Molecular vision.

[80]  N. Osborne,et al.  Oxidative-induced retinal degeneration is attenuated by epigallocatechin gallate , 2006, Brain Research.

[81]  P. Campochiaro,et al.  Reduction of p66Shc suppresses oxidative damage in retinal pigmented epithelial cells and retina , 2006, Journal of cellular physiology.

[82]  A. Holmgren,et al.  The thioredoxin system in cancer. , 2006, Seminars in cancer biology.

[83]  I. Matias,et al.  Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of patients with diabetic retinopathy and age-related macular degeneration. , 2006, Prostaglandins, leukotrienes, and essential fatty acids.

[84]  K. Eng,et al.  Ranibizumab in neovascular age-related macular degeneration , 2006, Clinical interventions in aging.

[85]  S. Seal,et al.  Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides , 2006, Nature nanotechnology.

[86]  C Gélinas,et al.  Current insights into the regulation of programmed cell death by NF-κB , 2006, Oncogene.

[87]  Susan Schneider,et al.  Ranibizumab versus verteporfin for neovascular age-related macular degeneration. , 2006, The New England journal of medicine.

[88]  N. Orr,et al.  A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration , 2006, Nature Genetics.

[89]  J. Sears,et al.  Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration , 2006, Proceedings of the National Academy of Sciences.

[90]  Kei Shinoda,et al.  Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[91]  J. Simon,et al.  Effects of Photodegradation on the Physical and Antioxidant Properties of Melanosomes Isolated from Retinal Pigment Epithelium , 2006, Photochemistry and photobiology.

[92]  K. Bartz-Schmidt,et al.  Melanin Protects Choroidal Blood Vessels against Light Toxicity , 2006, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[93]  D. Shanmuganayagam,et al.  Measurement of regional choroidal blood flow in rabbits and monkeys using fluorescent microspheres. , 2006, Archives of ophthalmology.

[94]  A. Quattrone,et al.  Curcumin activates defensive genes and protects neurons against oxidative stress. , 2006, Antioxidants & redox signaling.

[95]  J. Haines,et al.  Cigarette smoking strongly modifies the association of LOC387715 and age-related macular degeneration. , 2006, American journal of human genetics.

[96]  K. Gumus,et al.  Plasma homocysteine, vitamin B12 and folate levels in age-related macular degeneration , 2006, Graefe's Archive for Clinical and Experimental Ophthalmology.

[97]  Usha Chakravarthy,et al.  Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE). , 2006, Archives of ophthalmology.

[98]  R. T. Smith,et al.  Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration , 2006, Nature Genetics.

[99]  E. Gaillard,et al.  Antioxidant Properties of Melanin in Retinal Pigment Epithelial Cells , 2006, Photochemistry and photobiology.

[100]  R. Raman,et al.  Plasma homocysteine and total thiol content in patients with exudative age-related macular degeneration , 2006, Eye.

[101]  Don H. Anderson,et al.  Extended haplotypes in the complement factor H (CFH) and CFH‐related (CFHR) family of genes protect against age‐related macular degeneration: Characterization, ethnic distribution and evolutionary implications , 2006, Annals of medicine.

[102]  D. Clayton,et al.  Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation , 2005, British Journal of Ophthalmology.

[103]  S. Karakucuk,et al.  Serum Paraoxonase 1 Activity and Lipid Peroxidation Levels in Patients with Age-Related Macular Degeneration , 2005, Ophthalmologica.

[104]  A. Swaroop,et al.  Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. , 2005, Ophthalmology.

[105]  E. Świętochowska,et al.  Homocysteine, Vitamin B12, and Folic Acid in Age-Related Macular Degeneration , 2005, European journal of ophthalmology.

[106]  Y. Ho,et al.  SOD2 protects against oxidation-induced apoptosis in mouse retinal pigment epithelium: implications for age-related macular degeneration. , 2005, Investigative ophthalmology & visual science.

[107]  D. Hinton,et al.  Protection from oxidative stress by methionine sulfoxide reductases in RPE cells. , 2005, Biochemical and biophysical research communications.

[108]  C. Giulivi,et al.  Superoxide dismutases and their impact upon human health. , 2005, Molecular aspects of medicine.

[109]  M. Rambeau,et al.  Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age-related macular degeneration patients. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[110]  J. Gilbert,et al.  Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration , 2005, Science.

[111]  F. V. van Kuijk,et al.  Toxicity and detoxification of lipid-derived aldehydes in cultured retinal pigmented epithelial cells. , 2005, Toxicology and applied pharmacology.

[112]  A. Edwards,et al.  Complement Factor H Polymorphism and Age-Related Macular Degeneration , 2005, Science.

[113]  J. Ott,et al.  Complement Factor H Polymorphism in Age-Related Macular Degeneration , 2005, Science.

[114]  I. Young,et al.  Association study of detoxification genes in age related macular degeneration , 2005, British Journal of Ophthalmology.

[115]  Dean P. Jones,et al.  Oxidant-induced apoptosis in human retinal pigment epithelial cells: dependence on extracellular redox state. , 2005, Investigative ophthalmology & visual science.

[116]  J. Bomser,et al.  Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition. , 2005, Chemico-biological interactions.

[117]  S. Resnikoff,et al.  Global data on visual impairment in the year 2002. , 2004, Bulletin of the World Health Organization.

[118]  J. Bennett,et al.  Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress. , 2004, Human gene therapy.

[119]  T. Cotter,et al.  Oxidative Stress-induced Apoptosis in Retinal Photoreceptor Cells Is Mediated by Calpains and Caspases and Blocked by the Oxygen Radical Scavenger CR-6* , 2004, Journal of Biological Chemistry.

[120]  J. Campisi,et al.  Telomere length mediates the effects of telomerase on the cellular response to genotoxic stress. , 2004, Experimental cell research.

[121]  P. Talalay,et al.  Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[122]  A-K Dubey,et al.  Ginkgo biloba--an appraisal. , 2004, Kathmandu University medical journal.

[123]  R. Klein,et al.  Location of lesions associated with age-related maculopathy over a 10-year period: the Beaver Dam Eye Study. , 2004, Investigative ophthalmology & visual science.

[124]  B. Munoz,et al.  Racial variations in causes of vision loss in nursing homes: The Salisbury Eye Evaluation in Nursing Home Groups (SEEING) Study. , 2004, Archives of ophthalmology.

[125]  Cindy Wang,et al.  Melatonin protects human retinal pigment epithelial (RPE) cells against oxidative stress. , 2004, Experimental eye research.

[126]  Shih-Jen Chen,et al.  Different Plasma Levels of Vascular Endothelial Growth Factor and Nitric Oxide between Patients with Choroidal and Retinal Neovascularization , 2004, Ophthalmologica.

[127]  L. Tamer,et al.  Changes in Antioxidant Enzyme Activity and Malondialdehyde Level in Patients with Age-Related Macular Degeneration , 2004, Ophthalmologica.

[128]  P. Jong Prevalence of age-related macular degeneration in the United States. , 2004 .

[129]  M. Miyagi,et al.  Carboxyethylpyrrole Protein Adducts and Autoantibodies, Biomarkers for Age-related Macular Degeneration* , 2003, Journal of Biological Chemistry.

[130]  Keyang Wang,et al.  Caloric restriction retards age-related changes in rat retina. , 2003, Biochemical and biophysical research communications.

[131]  J. Kopitz,et al.  Proteins modified by malondialdehyde, 4-hydroxynonenal, or advanced glycation end products in lipofuscin of human retinal pigment epithelium. , 2003, Investigative ophthalmology & visual science.

[132]  A. Dinkova-Kostova,et al.  Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. , 2003, Advances in enzyme regulation.

[133]  S. Jockusch,et al.  A2E-epoxides Damage DNA in Retinal Pigment Epithelial Cells , 2003, The Journal of Biological Chemistry.

[134]  R. Klein,et al.  Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam Eye Study. , 2003, Archives of ophthalmology.

[135]  S. Hazen,et al.  Oxidatively truncated docosahexaenoate phospholipids: total synthesis, generation, and Peptide adduction chemistry. , 2003, The Journal of organic chemistry.

[136]  Y. Turkoz,et al.  Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration , 2003, Documenta Ophthalmologica.

[137]  Masaru Miyagi,et al.  Drusen proteome analysis: An approach to the etiology of age-related macular degeneration , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[138]  R. Klein,et al.  Relation of blood homocysteine and its nutritional determinants to age-related maculopathy in the third National Health and Nutrition Examination Survey. , 2002, The American journal of clinical nutrition.

[139]  F. Testa,et al.  Serum oxidative and antioxidant parameters in a group of Italian patients with age-related maculopathy. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[140]  B. Godley,et al.  Bcl-2 overexpression increases survival in human retinal pigment epithelial cells exposed to H(2)O(2). , 2002, Experimental eye research.

[141]  M. Tanito,et al.  Cytoprotective effect of thioredoxin against retinal photic injury in mice. , 2002, Investigative ophthalmology & visual science.

[142]  O. Çekiç,et al.  Plasma malondialdehyde and nitric oxide levels in age related macular degeneration , 2001, The British journal of ophthalmology.

[143]  Elias S. J. Arnér,et al.  Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. , 2001, Free radical biology & medicine.

[144]  F. A. Shamsi,et al.  Inhibition of RPE lysosomal and antioxidant activity by the age pigment lipofuscin. , 2001, Investigative ophthalmology & visual science.

[145]  N. Ishii [The role of oxidative stress in ageing]. , 2001, Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics.

[146]  S. Melov,et al.  Mitochondrial DNA mutations, oxidative stress, and aging , 2001, Mechanisms of Ageing and Development.

[147]  V. Serra,et al.  Accelerated telomere shortening in Fanconi anemia fibroblasts – a longitudinal study , 2001, FEBS letters.

[148]  T. Yoshikawa,et al.  Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration. , 2001, American journal of ophthalmology.

[149]  S. Nilsson,et al.  Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants. , 2001, Free radical biology & medicine.

[150]  J. Sparrow,et al.  Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl-2. , 2001, Investigative ophthalmology & visual science.

[151]  S. Sonoda,et al.  Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. , 2000, American journal of ophthalmology.

[152]  K. Nakanishi,et al.  The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. , 2000, Investigative ophthalmology & visual science.

[153]  L. Rapp,et al.  Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina. , 2000, Investigative ophthalmology & visual science.

[154]  Dean P. Jones,et al.  Oxidative damage and protection of the RPE , 2000, Progress in Retinal and Eye Research.

[155]  C. Scheidereit,et al.  NF-kappaB and the innate immune response. , 2000, Current opinion in immunology.

[156]  D. Valle,et al.  Online Mendelian Inheritance In Man (OMIM) , 2000, Human mutation.

[157]  Pier Paolo Pandolfi,et al.  The p66shc adaptor protein controls oxidative stress response and life span in mammals , 1999, Nature.

[158]  S. Davies,et al.  The Photoreactivity of the Retinal Age Pigment Lipofuscin* , 1999, The Journal of Biological Chemistry.

[159]  R. Frank,et al.  Antioxidant enzymes in the macular retinal pigment epithelium of eyes with neovascular age-related macular degeneration. , 1999, American journal of ophthalmology.

[160]  B. Godley,et al.  Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells. , 1999, Experimental eye research.

[161]  C. Delcourt,et al.  Associations of antioxidant enzymes with cataract and age-related macular degeneration. The POLA Study. Pathologies Oculaires Liées à l'Age. , 1999, Ophthalmology.

[162]  M. Prevost,et al.  Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process , 1999, The Journal of experimental medicine.

[163]  G. Kutty,et al.  Light history and age-related changes in retinal light damage. , 1998, Investigative ophthalmology & visual science.

[164]  S. Marklund,et al.  Superoxide dismutase isoenzymes in the human eye. , 1998, Investigative ophthalmology & visual science.

[165]  F. Khachik,et al.  Identification of lutein and zeaxanthin oxidation products in human and monkey retinas. , 1997, Investigative ophthalmology & visual science.

[166]  I. Shami Smoking and age-related maculopathy , 1997 .

[167]  P Darzins,et al.  Sun exposure and age-related macular degeneration. An Australian case-control study. , 1997, Ophthalmology.

[168]  Dean P. Jones,et al.  Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked , 1997, Science.

[169]  R. Bone,et al.  Distribution of lutein and zeaxanthin stereoisomers in the human retina. , 1997, Experimental eye research.

[170]  P. D. de Jong,et al.  Increased expression of angiogenic growth factors in age-related maculopathy , 1997, The British journal of ophthalmology.

[171]  M R Cullen,et al.  Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. , 1996, Journal of the National Cancer Institute.

[172]  I. Fridovich,et al.  Red blood cell antioxidant enzymes in age-related macular degeneration. , 1996, The British journal of ophthalmology.

[173]  R. Klein,et al.  Serum antioxidants and age-related macular degeneration in a population-based case-control study. , 1995, Archives of ophthalmology.

[174]  B. Aggarwal,et al.  Activation of Transcription Factor NF-κB Is Suppressed by Curcumin (Diferuloylmethane) (*) , 1995, The Journal of Biological Chemistry.

[175]  T. Kaneko,et al.  Relevance of oxidative stress to the limited replicative capacity of cultured human diploid cells: the limit of cumulative population doublings increases under low concentrations of oxygen and decreases in response to aminotriazole , 1995, Mechanisms of Ageing and Development.

[176]  B. Aggarwal,et al.  The p60 Tumor Necrosis Factor (TNF) Receptor-associated Kinase (TRAK) Binds Residues 344–397 within the Cytoplasmic Domain Involved in TNF Signaling (*) , 1995, The Journal of Biological Chemistry.

[177]  G. Chader,et al.  Induction of heme oxygenase 1 in the retina by intense visible light: suppression by the antioxidant dimethylthiourea. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[178]  W. Feuer,et al.  Low glutathione reductase and peroxidase activity in age-related macular degeneration. , 1994, The British journal of ophthalmology.

[179]  M. Liles,et al.  Evaluation of oxidative processes in human pigment epithelial cells associated with retinal outer segment phagocytosis. , 1994, Experimental cell research.

[180]  L. Packer Antioxidant Action of Carotenoids in Vitro and in Vivo and Protection against Oxidation of Human Low‐Density Lipoproteins a , b , 1993, Annals of the New York Academy of Sciences.

[181]  R. Klein,et al.  Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. , 1993, Archives of ophthalmology.

[182]  R. Nath,et al.  Antioxidant enzymes in RBCs as a biological index of age related macular degeneration , 1993, Acta ophthalmologica.

[183]  D. DeMets,et al.  The Beaver Dam Eye Study: the relation of age-related maculopathy to smoking. , 1993, American journal of epidemiology.

[184]  F. V. van Kuijk,et al.  Fatty acid composition of the human macula and peripheral retina. , 1992, Investigative ophthalmology & visual science.

[185]  B. P. Lim,et al.  Antioxidant activity of xanthophylls on peroxyl radical-mediated phospholipid peroxidation. , 1992, Biochimica et biophysica acta.

[186]  V. Sorrenti,et al.  Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age , 1992, Neurochemical Research.

[187]  M. Liles,et al.  Antioxidant enzymes in the aging human retinal pigment epithelium. , 1991, Archives of ophthalmology.

[188]  L. Bynoe,et al.  Hematogenous photosensitization. A mechanism for the development of age-related macular degeneration. , 1990, Investigative ophthalmology & visual science.

[189]  B. Munoz,et al.  Exposure to sunlight and other risk factors for age-related macular degeneration. , 1989, Archives of ophthalmology.

[190]  M. Iwasaki,et al.  Lipofuscin granules in human photoreceptor cells. , 1988, Investigative ophthalmology & visual science.

[191]  D. Newsome,et al.  Macular degeneration and elevated serum ceruloplasmin. , 1986, Investigative ophthalmology & visual science.

[192]  B Chance,et al.  Hydroperoxide metabolism in mammalian organs. , 1979, Physiological reviews.

[193]  J. Weiter,et al.  The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. , 1978, Investigative ophthalmology & visual science.

[194]  L. Hayflick,et al.  The serial cultivation of human diploid cell strains. , 1961, Experimental cell research.

[195]  W. O. Lundberg Lipids of biologic importance; peroxidation products and inclusion compounds of lipids. , 1958, The American journal of clinical nutrition.

[196]  D. Harman Aging: a theory based on free radical and radiation chemistry. , 1956, Journal of gerontology.

[197]  S. Ennis,et al.  Support for the involvement of complement factor I in age-related macular degeneration , 2010, European Journal of Human Genetics.

[198]  M. Wolzt,et al.  Effects of antioxidants (AREDS medication) on ocular blood flow and endothelial function in an endotoxin-induced model of oxidative stress in humans. , 2010, Investigative ophthalmology & visual science.

[199]  M. Lenardo,et al.  The nuclear signaling of NF-κB: current knowledge, new insights, and future perspectives , 2010, Cell Research.

[200]  M. Daly,et al.  Variation near complement factor I is associated with risk of advanced AMD , 2009, European Journal of Human Genetics.

[201]  A. Kızıltunç,et al.  Decreased serum paraoxonase 1 activity and increased serum homocysteine and malondialdehyde levels in age-related macular degeneration. , 2009, The Tohoku journal of experimental medicine.

[202]  E. Onaivi Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications. , 2009, International review of neurobiology.

[203]  J. Vander Association between the SERPING1 gene and age-related macular degeneration: a two-stage case–control study , 2009 .

[204]  D. Ingram,et al.  Dietary restriction in aging nonhuman primates. , 2007, Interdisciplinary topics in gerontology.

[205]  B. Ames,et al.  Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid. , 2007, Investigative ophthalmology & visual science.

[206]  P.T.V.M. de Jong,et al.  Mechanisms of disease: Age-related macular degeneration , 2006 .

[207]  R. Milton,et al.  Evaluation of plasma homocysteine and risk of age-related macular degeneration. , 2006, American journal of ophthalmology.

[208]  A. Ramé [Age-related macular degeneration]. , 2006, Revue de l'infirmiere.

[209]  O. Schein,et al.  Sunlight and Age-Related Macular Degeneration , 2005, International ophthalmology clinics.

[210]  D. Weeks,et al.  Susceptibility genes for age-related maculopathy on chromosome 10q26. , 2005, American journal of human genetics.

[211]  Lars G Fritsche,et al.  Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. , 2005, Human molecular genetics.

[212]  Robert F Bonner,et al.  A model of spectral filtering to reduce photochemical damage in age-related macular degeneration. , 2004, Transactions of the American Ophthalmological Society.

[213]  Y. Benjamini,et al.  Association of neovascular age-related macular degeneration and hyperhomocysteinemia. , 2004, American journal of ophthalmology.

[214]  U. Brunk,et al.  Aging of cultured retinal pigment epithelial cells: oxidative reactions, lipofuscin formation and blue light damage , 2004, Documenta Ophthalmologica.

[215]  A. Young,et al.  Antioxidant and prooxidant properties of carotenoids. , 2001, Archives of biochemistry and biophysics.

[216]  Jennifer I. Lim,et al.  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. , 2001, Archives of ophthalmology.

[217]  M. Boulton,et al.  Retinal photodamage. , 2001, Journal of photochemistry and photobiology. B, Biology.

[218]  P. Talalay Chemoprotection against cancer by induction of phase 2 enzymes. , 2000, BioFactors.

[219]  T. Horie,et al.  Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. , 1999, Pharmacological research.

[220]  P. Mayeux,et al.  Biology of erythropoietin. , 1998, Haematologica.

[221]  P. Mitchell,et al.  Smoking and age-related maculopathy. The Blue Mountains Eye Study. , 1996, Archives of ophthalmology.

[222]  J. Vingerling,et al.  Age-related macular degeneration and smoking. The Rotterdam Study. , 1996, A M A Archives of Ophthalmology.

[223]  B. Aggarwal,et al.  Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. , 1995, The Journal of biological chemistry.

[224]  W. Jelkmann,et al.  Biology of erythropoietin. , 1994, The Clinical investigator.

[225]  R. Klein,et al.  The Beaver Dam Eye Study. Retinopathy in adults with newly discovered and previously diagnosed diabetes mellitus. , 1992, Ophthalmology.

[226]  T. Hirano,et al.  LIGHT-INDUCED RETINAL DAMAGE IN MICE: Hydrogen Peroxide Production and Superoxide Dismutase Activity in Retina , 1992, Retina.

[227]  B. Munoz,et al.  Visible light and risk of age-related macular degeneration. , 1990, Transactions of the American Ophthalmological Society.

[228]  S. Fliesler,et al.  Chemistry and metabolism of lipids in the vertebrate retina. , 1983, Progress in lipid research.