Functional and morphological evaluation of blue light-emitting diode-induced retinal degeneration in mice

PurposeThe purpose of this study was to evaluate a retinal degeneration (RD) model induced by exposing mice to a blue light-emitting diode (LED), which led to photoreceptor cell death.MethodsRD was induced in BALB/c mice by exposure to a blue LED (460 nm) for 2 hours. Retinal function was examined using scotopic electroretinography (ERG). Histopathological changes were assessed by hematoxylin and eosin (H&E) staining and electron microscopy. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In addition, retinal inflammation and oxidative stress were evaluated by immunohistochemistry with anti-glial fibrillary acidic protein (GFAP) and anti-8-hydroxy-2’-deoxyguanosine (8-OHdG), respectively.ResultsScotopic ERG showed that blue LED exposure resulted in a decrease in both a-waves and b-waves in mice retinas in an illuminance-dependent manner. H&E, TUNEL assay, and electron microscopy revealed massive photoreceptor cell death by apoptosis in the central region of the retina. Retinal stress and inflammation were detected by increased expression of GFAP and by electron microscopy findings demonstrating microglia infiltration in the outer nuclear layer and subretinal space. In addition, increased labeling of 8-OHdG was observed in the retinas from blue LED exposure.ConclusionsThese results suggest that blue LED-induced RD may be a useful animal model in which to study the pathogenesis of RD, including age-related macular degeneration, and to evaluate the effects of new therapeutic agents prior to clinical trials, where oxidative stress and inflammation are the underlying RD mechanisms.

[1]  W. Markesbery,et al.  Oxidative Alterations in Alzheimer's Disease , 1999, Brain pathology.

[2]  F. Delori Introducing Charlotte Remé, the 2004 Recipient of the Proctor Medal , 2005 .

[3]  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.

[4]  F. Parmeggiani,et al.  Mechanism of Inflammation in Age-Related Macular Degeneration , 2012, Mediators of inflammation.

[5]  J. Lombardini,et al.  Age-Related Retinal Degeneration in Animal Models of Aging: Possible Involvement of Taurine Deficiency and Oxidative Stress , 2004, Neurochemical Research.

[6]  J. Windle,et al.  Death at an early age. Apoptosis in inherited retinal degenerations. , 1995, Investigative ophthalmology & visual science.

[7]  B. Jones,et al.  Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration , 2008, Molecular vision.

[8]  A. Basu,et al.  Modulation of interleukin-1β mediated inflammatory response in human astrocytes by flavonoids: Implications in neuroprotection , 2007, Brain Research Bulletin.

[9]  H. Hara,et al.  Damage of photoreceptor-derived cells in culture induced by light emitting diode-derived blue light , 2014, Scientific Reports.

[10]  L. Liaudet,et al.  The role of oxidative stress during inflammatory processes , 2013, Biological chemistry.

[11]  Tiansen Li,et al.  Retinal degeneration in the rd mouse is caused by a defect in the β subunit of rod cGMP-phosphodiesterase , 1990, Nature.

[12]  S. W. Jung,et al.  Cyanidin-3-glucoside Extracted from Mulberry Fruit Can Reduce N-methyl-N-nitrosourea-Induced Retinal Degeneration in Rats , 2013, Current eye research.

[13]  A. Fletcher Free Radicals, Antioxidants and Eye Diseases: Evidence from Epidemiological Studies on Cataract and Age-Related Macular Degeneration , 2010, Ophthalmic Research.

[14]  S. Qiu,et al.  Neuroglobin – A potential biological marker of retinal damage induced by LED light , 2014, Neuroscience.

[15]  G. Zissis,et al.  Light-emitting diodes (LED) for domestic lighting: Any risks for the eye? , 2011, Progress in Retinal and Eye Research.

[16]  A. Wyllie,et al.  Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics , 1972, British Journal of Cancer.

[17]  K. Gregory-Evans,et al.  Genetic blindness: current concepts in the pathogenesis of human outer retinal dystrophies. , 1998, Trends in genetics : TIG.

[18]  S. Sanyal,et al.  Development and degeneration of retina in rds mutant mice: Light microscopy , 1980, The Journal of comparative neurology.

[19]  O'Callaghan Jp Assessment of neurotoxicity: use of glial fibrillary acidic protein as a biomarker. , 1991 .

[20]  H. Hara,et al.  Protective effects of bilberry and lingonberry extracts against blue light-emitting diode light-induced retinal photoreceptor cell damage in vitro , 2014, BMC Complementary and Alternative Medicine.

[21]  W. Green,et al.  Histopathology of age-related macular degeneration. , 1999, Molecular vision.

[22]  P. Debré,et al.  CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. , 2007, The Journal of clinical investigation.

[23]  A. Sorsby EXPERIMENTAL PIGMENTARY DEGENERATION OF THE RETINA BY SODIUM IODATE , 1941, The British journal of ophthalmology.

[24]  A. Milam,et al.  Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. , 2003, Experimental eye research.

[25]  C. Grimm,et al.  Apoptotic cell death in retinal degenerations , 1998, Progress in Retinal and Eye Research.

[26]  C. Remé The dark side of light: rhodopsin and the silent death of vision the proctor lecture. , 2005, Investigative ophthalmology & visual science.

[27]  Greene Wr Histopathology of age-related macular degeneration. , 1999, Molecular vision.

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

[29]  Chang-Hao Yang,et al.  White Light–Emitting Diodes (LEDs) at Domestic Lighting Levels and Retinal Injury in a Rat Model , 2013, Environmental health perspectives.

[30]  L. Wheeler,et al.  A Novel In Vivo Model of Focal Light Emitting Diode-Induced Cone-Photoreceptor Phototoxicity: Neuroprotection Afforded by Brimonidine, BDNF, PEDF or bFGF , 2014, PloS one.

[31]  J. B. Lopes de Faria,et al.  Arterial hypertension exacerbates oxidative stress in early diabetic retinopathy , 2007, Free radical research.

[32]  O'Callaghan Jp,et al.  Assessment of neurotoxicity: use of glial fibrillary acidic protein as a biomarker. , 1991, Biomedical and environmental sciences : BES.

[33]  Johanna M. Seddon,et al.  The Epidemiology of Age-Related Macular Degeneration , 2004, International ophthalmology clinics.

[34]  Wai T Wong,et al.  Ex vivo dynamic imaging of retinal microglia using time-lapse confocal microscopy. , 2008, Investigative ophthalmology & visual science.

[35]  M. Chun,et al.  Reaction of Müller cells after increased intraocular pressure in the rat retina , 1998, Experimental Brain Research.

[36]  K. Herrold Pigmentary degeneration of the retina induced by N-methyl-N-nitrosourea. An experimental study in syrian hamsters. , 1967, Archives of ophthalmology.

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

[38]  J. Dunaief,et al.  Systemic administration of the antioxidant/iron chelator α-lipoic acid protects against light-induced photoreceptor degeneration in the mouse retina. , 2014, Investigative ophthalmology & visual science.

[39]  Jeremy Nathans,et al.  Macular degeneration: recent advances and therapeutic opportunities , 2006, Nature Reviews Neuroscience.

[40]  S Berman,et al.  Retinal damage by light in rats. , 1966, Investigative ophthalmology.

[41]  S. Kishi,et al.  Functional and morphologic consequences of light exposure in primate eyes. , 2012, Investigative ophthalmology & visual science.

[42]  S. W. Jung,et al.  Anthocyanins from the seed coat of black soybean reduce retinal degeneration induced by N-methyl-N-nitrosourea. , 2012, Experimental eye research.

[43]  P. Debré,et al.  CX 3 CR 1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration , 2007 .

[44]  Chi-Chao Chan,et al.  Molecular pathology of age-related macular degeneration , 2009, Progress in Retinal and Eye Research.

[45]  E. Chamorro,et al.  Effects of Light‐emitting Diode Radiations on Human Retinal Pigment Epithelial Cells In Vitro , 2013, Photochemistry and photobiology.

[46]  R. Sidman,et al.  Congenic strains of RCS rats with inherited retinal dystrophy. , 1975, The Journal of heredity.

[47]  Ronald Klein,et al.  The prevalence of age-related macular degeneration and associated risk factors. , 2001, Archives of ophthalmology.