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Author van der Burght, B.W.; Hansen, M.; Olsen, J.; Zhou, J.; Wu, Y.; Nissen, M.H.; Sparrow, J.R.
Title Early changes in gene expression induced by blue light irradiation of A2E-laden retinal pigment epithelial cells Type Journal Article
Year 2013 Publication Acta Ophthalmologica Abbreviated Journal Acta Ophthalmol
Volume 91 Issue 7 Pages e537-45
Keywords Apoptosis; Cell Line; Cell Survival; Gene Expression Regulation/*physiology; Humans; Light; Lipofuscin/genetics; Oligonucleotide Array Sequence Analysis; Principal Component Analysis; Pyridinium Compounds; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Retinal Pigment Epithelium/metabolism/pathology/*radiation effects; Retinoids/*genetics; Transcriptome; A2e; age-related macular degeneration; apoptosis; complement cascade; gene expression; retinal pigment epithelial cells; blue light; retinal pigment epithelial; epigenetics
Abstract PURPOSE: Accumulation of bisretinoids as lipofuscin in retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of some blinding diseases including age-related macular degeneration (AMD). To identify genes whose expression may change under conditions of bisretinoid accumulation, we investigated the differential gene expression in RPE cells that had accumulated the lipofuscin fluorophore A2E and were exposed to blue light (430 nm). METHODS: A2E-laden RPE cells were exposed to blue light (A2E/430 nm) at various time intervals. Cell death was quantified using Dead Red staining, and RNA levels for the entire genome was determined using DNA microarrays (Affymetrix GeneChip Human Genome 2.0 Plus). Array results for selected genes were confirmed by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Principal component analysis revealed that the A2E-laden RPE cells irradiated with blue light were clearly distinguishable from the control samples. We found differential regulation of genes belonging to the following functional groups: transcription factors, stress response, apoptosis and immune response. Among the last mentioned were downregulation of four genes that coded for proteins that have an inhibitory effect on the complement cascade: (complement factor H, complement factor H-related 1, complement factor I and vitronectin) and of two belonging to the classical pathway (complement component 1, s subcomponent and complement component 1, r subcomponent). CONCLUSION: This study demonstrates that blue light irradiation of A2E-laden RPE cells can alter the transcription of genes belonging to different functional pathways including stress response, apoptosis and the immune response. We suggest that these molecules may be associated to the pathogenesis of AMD and can potentially serve as future therapeutic targets.
Address (up) Department of International Health, Immunology and Microbiology, Eye Research Unit, University of Copenhagen, Copenhagen, DenmarkDepartment of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DenmarkDepartment of Ophthalmology, Columbia University, New York, New York, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1755-375X ISBN Medium
Area Expedition Conference
Notes PMID:23742627 Approved no
Call Number IDA @ john @ Serial 346
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Author Yasuniwa, Y.; Izumi, H.; Wang, K.-Y.; Shimajiri, S.; Sasaguri, Y.; Kawai, K.; Kasai, H.; Shimada, T.; Miyake, K.; Kashiwagi, E.; Hirano, G.; Kidani, A.; Akiyama, M.; Han, B.; Wu, Y.; Ieiri, I.; Higuchi, S.; Kohno, K.
Title Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway Type Journal Article
Year 2010 Publication PloS one Abbreviated Journal PLoS One
Volume 5 Issue 12 Pages e15330
Keywords Animals; *Circadian Rhythm; Disease Progression; *Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms/*pathology; *Neovascularization, Pathologic; Nerve Tissue Proteins/metabolism; Skin/metabolism; Vascular Endothelial Growth Factor A/metabolism; Wnt Proteins/*metabolism; Oncogenesis
Abstract Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway.
Address (up) Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1932-6203 ISBN Medium
Area Expedition Conference
Notes PMID:21203463; PMCID:PMC3009728 Approved no
Call Number IDA @ john @ Serial 162
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Author Brainard, G.C.; Sliney, D.; Hanifin, J.P.; Glickman, G.; Byrne, B.; Greeson, J.M.; Jasser, S.; Gerner, E.; Rollag, M.D.
Title Sensitivity of the human circadian system to short-wavelength (420-nm) light Type Journal Article
Year 2008 Publication Journal of Biological Rhythms Abbreviated Journal J Biol Rhythms
Volume 23 Issue 5 Pages 379-386
Keywords Human Health; Adult; Circadian Rhythm/*radiation effects; Female; Humans; *Light; Male; Melatonin/metabolism; Models, Biological; Neurosecretory Systems; Photons; Pineal Gland/metabolism; Retinal Ganglion Cells/*metabolism; Vision, Ocular
Abstract The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.
Address (up) Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. george.brainard@jefferson.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0748-7304 ISBN Medium
Area Expedition Conference
Notes PMID:18838601 Approved no
Call Number LoNNe @ kagoburian @ Serial 724
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Author Lucas, R.J.; Peirson, S.N.; Berson, D.M.; Brown, T.M.; Cooper, H.M.; Czeisler, C.A.; Figueiro, M.G.; Gamlin, P.D.; Lockley, S.W.; O'Hagan, J.B.; Price, L.L.A.; Provencio, I.; Skene, D.J.; Brainard, G.C.
Title Measuring and using light in the melanopsin age Type Journal Article
Year 2014 Publication Trends in Neurosciences Abbreviated Journal Trends Neurosci
Volume 37 Issue 1 Pages 1-9
Keywords Editorial; Animals; Circadian Rhythm/physiology; Humans; Photoreceptor Cells/metabolism; Phototherapy/*trends; Retinal Ganglion Cells/metabolism; Rod Opsins/*physiology
Abstract Light is a potent stimulus for regulating circadian, hormonal, and behavioral systems. In addition, light therapy is effective for certain affective disorders, sleep problems, and circadian rhythm disruption. These biological and behavioral effects of light are influenced by a distinct photoreceptor in the eye, melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to conventional rods and cones. We summarize the neurophysiology of this newly described sensory pathway and consider implications for the measurement, production, and application of light. A new light-measurement strategy taking account of the complex photoreceptive inputs to these non-visual responses is proposed for use by researchers, and simple suggestions for artificial/architectural lighting are provided for regulatory authorities, lighting manufacturers, designers, and engineers.
Address (up) Department of Neurology, Thomas Jefferson University, Philidelphia, PA, USA. Electronic address: George.Brainard@jefferson.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0166-2236 ISBN Medium
Area Expedition Conference
Notes PMID:24287308 Approved no
Call Number LoNNe @ christopher.kyba @ Serial 457
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Author Berson, D.M.; Dunn, F.A.; Takao, M.
Title Phototransduction by retinal ganglion cells that set the circadian clock Type Journal Article
Year 2002 Publication Science (New York, N.Y.) Abbreviated Journal Science
Volume 295 Issue 5557 Pages 1070-1073
Keywords Human Health; Animals; Axons/ultrastructure; *Biological Clocks; *Circadian Rhythm; Dendrites/ultrastructure; Isoquinolines; Kinetics; Light; *Light Signal Transduction; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells/chemistry/cytology/*physiology; Rod Opsins/analysis/physiology; Suprachiasmatic Nucleus/cytology/*physiology
Abstract Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
Address (up) Department of Neuroscience, Brown University, Providence, RI, 02912 USA. David_Berson@brown.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0036-8075 ISBN Medium
Area Expedition Conference
Notes PMID:11834835 Approved no
Call Number LoNNe @ kagoburian @ Serial 720
Permanent link to this record