The influence of sublethal blue light exposure on human RPE cells

Purpose To evaluate the in vitro response of retinal pigment epithelial (RPE) cells to a nonlethal dose of blue light. Methods The human RPE cell line ARPE-19 was irradiated with blue light (405 nm) at an output power of 1 mW/cm2 or 0.3 mW/cm2. The following parameters were studied: metabolic activity; apoptosis; reactive oxygen species (ROS) production; mitochondrial membrane potential (MMP); ultrastructural changes of mitochondria; production of advanced glycation endproducts (AGEs); and stress-related cellular proteins. Results Nonlethal doses of blue light irradiation significantly reduced ARPE-19 metabolic activity and MMP while increasing intracellular ROS levels and expression of stress-related proteins heme oxygenase-1 (HO-1), osteopontin, heat shock protein 27 (Hsp-27), manganese superoxide dismutase (SOD-Mn), and cathepsin D. Blue light irradiation also induced ultrastructural conformation changes in mitochondria, resulting in the appearance of giant mitochondria after 72 h. We further found enhanced formation of AGEs, particularly Nε-(carboxymethyl) lysine (CML) modifications, and a delay in the cell cycle. Conclusions ARPE-19 cells avoid cell death and recover from blue light irradiation by activating a host of defense mechanisms while simultaneously triggering cellular stress responses that may be involved in RPE disease development. Continuous light exposure can therefore detrimentally affect metabolically stressed RPE cells. This may have implications for pathogenesis of age-related macular degeneration.

[1]  Guang-Yu Li,et al.  Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies , 2008, Journal of neurochemistry.

[2]  A. Pawlak,et al.  Advanced Glycation as a Basis for Understanding Retinal Aging and Noninvasive Risk Prediction , 2008, Annals of the New York Academy of Sciences.

[3]  J. Norris,et al.  AcrySof Natural filter decreases blue light-induced apoptosis in human retinal pigment epithelium , 2008, Graefe's Archive for Clinical and Experimental Ophthalmology.

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

[5]  T. M. Calonge,et al.  Turning off the G2 DNA damage checkpoint. , 2008, DNA repair.

[6]  P. Jeggo,et al.  An Imperfect G2M Checkpoint Contributes to Chromosome Instability Following Irradiation of S and G2 Phase Cells , 2007, Cell cycle.

[7]  Brigitte Graf,et al.  Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells. , 2007, Investigative ophthalmology & visual science.

[8]  N. Osborne,et al.  Visible light affects mitochondrial function and induces neuronal death in retinal cell cultures , 2007, Vision Research.

[9]  N. Osborne,et al.  The influence of visible light exposure on cultured RGC-5 cells , 2007, Molecular vision.

[10]  W. Mieler,et al.  Photoprotection of human retinal pigment epithelium cells against blue light-induced apoptosis by melanin free radicals from Sepia officinalis , 2006, Proceedings of the National Academy of Sciences.

[11]  S. Oltjen,et al.  Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse. , 2006, Experimental eye research.

[12]  J. Handa,et al.  The expression of advanced glycation endproduct receptors in rpe cells associated with basal deposits in human maculas. , 2006, Experimental eye research.

[13]  Jawed Alam,et al.  Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. , 2006, Physiological reviews.

[14]  R. Funk,et al.  Inhibition of apoptosis and reduction of intracellular pH decrease in retinal neural cell cultures by a blocker of carbonic anhydrase. , 2006, Investigative ophthalmology & visual science.

[15]  J. Marshall,et al.  Age-related maculopathy and the impact of blue light hazard. , 2006, Acta ophthalmologica Scandinavica.

[16]  N. Osborne,et al.  A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies , 2006, British Journal of Ophthalmology.

[17]  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.

[18]  J. Norris,et al.  Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  B. Godley,et al.  Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells* , 2005, Journal of Biological Chemistry.

[20]  C. Grimm,et al.  Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration , 2005, Progress in Retinal and Eye Research.

[21]  M. Boulton,et al.  Do blue light filters confer protection against age-related macular degeneration? , 2004, Progress in Retinal and Eye Research.

[22]  Eyal Gottlieb,et al.  Mitochondria‐derived Reactive Oxygen Species Mediate Blue Light‐induced Death of Retinal Pigment Epithelial Cells ¶ , 2004, Photochemistry and photobiology.

[23]  A. Prigent-Tessier,et al.  Differential MnSOD and HO-1 expression in cerebral endothelial cells in response to sublethal oxidative stress , 2004, Brain Research.

[24]  Guido Kroemer,et al.  Mitochondrial control of apoptosis: an introduction. , 2003, Biochemical and biophysical research communications.

[25]  B. Godley,et al.  Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. , 2003, Experimental eye research.

[26]  I. Constable,et al.  Progressive age-related changes similar to age-related macular degeneration in a transgenic mouse model. , 2002, The American journal of pathology.

[27]  K. Csaky,et al.  Regulated heat shock protein 27 expression in human retinal pigment epithelium. , 2001, Investigative ophthalmology & visual science.

[28]  R J Gonzalez,et al.  Evaluation of hepatic subcellular fractions for Alamar blue and MTT reductase activity. , 2001, Toxicology in vitro : an international journal published in association with BIBRA.

[29]  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.

[30]  A Hofman,et al.  Risk factors for age-related macular degeneration: Pooled findings from three continents. , 2001, Ophthalmology.

[31]  J. Handa,et al.  The use of hyperoxia to induce chronic mild oxidative stress in RPE cells in vitro. , 2001, Molecular vision.

[32]  P Rol,et al.  Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching. , 2001, Investigative ophthalmology & visual science.

[33]  I. Wilson,et al.  Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. , 2000, European journal of biochemistry.

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

[35]  H. Geerts,et al.  A rapid method for the evaluation of compounds with mitochondria-protective properties , 1999, Journal of Neuroscience Methods.

[36]  M. Jäättelä,et al.  Heat shock proteins as cellular lifeguards. , 1999, Annals of medicine.

[37]  E. Chen,et al.  Blue light induced apoptosis in rat retina , 1999, Eye.

[38]  Timothy A. Skimina,et al.  Activation of flavin-containing oxidases underlies light-induced production of H2O2 in mammalian cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[39]  C. Curcio,et al.  Basal linear deposit and large drusen are specific for early age-related maculopathy. , 1999, Archives of ophthalmology.

[40]  M. Karbowski,et al.  Free radical-induced megamitochondria formation and apoptosis. , 1999, Free radical biology & medicine.

[41]  C. Franceschi,et al.  JC‐1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess ΔΨ changes in intact cells: implications for studies on mitochondrial functionality during apoptosis , 1997, FEBS letters.

[42]  K. Ikeda,et al.  Photo-enhanced modification of human skin elastin in actinic elastosis by N(epsilon)-(carboxymethyl)lysine, one of the glycoxidation products of the Maillard reaction. , 1997, The Journal of investigative dermatology.

[43]  L. Bakeeva,et al.  Ultrastructural changes in chondriome of human lymphocytes after irradiation with He-Ne laser: appearance of giant mitochondria. , 1997, Journal of photochemistry and photobiology. B, Biology.

[44]  E. Schleicher,et al.  Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. , 1997, The Journal of clinical investigation.

[45]  J. V. van Best,et al.  Function and morphology of the retinal pigment epithelium after light‐induced damage , 1997, Microscopy research and technique.

[46]  Tiina I. Karu,et al.  Ultrastructural changes in chondriome of human lymphocytes after irradiation with HeNe laser: appearance of giant mitochondria , 1996, European Conference on Biomedical Optics.

[47]  T. Lyons,et al.  The Advanced Glycation End Product, N-(Carboxymethyl)lysine, Is a Product of both Lipid Peroxidation and Glycoxidation Reactions (*) , 1996, The Journal of Biological Chemistry.

[48]  L. Hjelmeland,et al.  ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. , 1996, Experimental eye research.

[49]  Paul J Thornalley,et al.  Mechanism of the degradation of non-enzymatically glycated proteins under physiological conditions. Studies with the model fructosamine, N epsilon-(1-deoxy-D-fructos-1-yl)hippuryl-lysine. , 1992, European journal of biochemistry.

[50]  G F Vrensen,et al.  Blood-retinal barrier dysfunction at the pigment epithelium induced by blue light. , 1992, Investigative ophthalmology & visual science.

[51]  R. Klein,et al.  Prevalence of age-related maculopathy. The Beaver Dam Eye Study. , 1992, Ophthalmology.

[52]  I Nicoletti,et al.  A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. , 1991, Journal of immunological methods.

[53]  M. Mainster Light and macular degeneration: A biophysical and clinical perspective , 1987, Eye.

[54]  J. Baynes,et al.  Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. , 1986, The Journal of biological chemistry.

[55]  R. Kohn,et al.  Effects of age and diabetes mellitus on the solubility and nonenzymatic glucosylation of human skin collagen. , 1981, The Journal of clinical investigation.

[56]  V. Skulachev Integrating functions of biomembranes. Problems of lateral transport of energy, metabolites and electrons. , 1980, Biochimica et biophysica acta.

[57]  L.,et al.  Glucosylation of human collagen in aging and diabetes mellitus. , 1980, The Journal of clinical investigation.

[58]  R. J. Wang,et al.  LETHAL EFFECT OF “DAYLIGHT” FLUORESCENT LIGHT ON HUMAN CELLS IN TISSUE‐CULTURE MEDIUM , 1975, Photochemistry and photobiology.

[59]  H. Niida,et al.  DNA damage checkpoints in mammals. , 2006, Mutagenesis.

[60]  Bradley T. Smith,et al.  Ultraviolet and Near-Blue Light Effects on the Eye , 2005, International ophthalmology clinics.

[61]  S. Ichinose,et al.  Blue light-induced apoptosis in cultured retinal pigment epithelium cells of the rat , 2001, Graefe's Archive for Clinical and Experimental Ophthalmology.

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

[63]  L. B. Chen,et al.  Mitochondrial membrane potential monitored by JC-1 dye. , 1995, Methods in enzymology.

[64]  F S Rosenthal,et al.  The long-term effects of visible light on the eye. , 1992, Archives of ophthalmology.