Lipofuscin is a photoinducible free radical generator

Boulton, Mike; Донцов, А. Е.; Jarvis-Evans, J.; Оstrovsky, М. А.; Svistunenko, Dimitri A.

doi:10.1016/1011-1344(93)87085-2

Cited by 190 publications

(109 citation statements)

References 9 publications

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“…The pre-feeding of RPE cells with lipofuscin may have caused low level DNA damage, thus initiating DNA repair mechanisms. We have previously shown that lipofuscin exhibits a low level generation of ROS under dark conditions (22). It has been demonstrated that oxidative stress can induce expression of DNA repair enzymes such as ApoE endonuclease and DNA polymerase (␤) in RPE cells (16,36).…”

Section: Discussionmentioning

confidence: 99%

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Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells

Godley

Shamsi

Liang

et al. 2005

Journal of Biological Chemistry

Self Cite

385

294

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Exposure of biological chromophores to ultraviolet radiation can lead to photochemical damage. However, the role of visible light, particularly in the blue region of the spectrum, has been largely ignored. To test the hypothesis that blue light is toxic to non-pigmented epithelial cells, confluent cultures of human primary retinal epithelial cells were exposed to visible light (390 -550 nm at 2.8 milliwatts/cm 2 ) for up to 6 h. A small loss of mitochondrial respiratory activity was observed at 6 h compared with dark-maintained cells, and this loss became greater with increasing time. To investigate the mechanism of cell loss, the damage to mitochondrial and nuclear genes was assessed using the quantitative PCR. Light exposure significantly damaged mitochondrial DNA at 3 h (0.7 lesion/10 kb DNA) compared with darkmaintained controls. However, by 6 h of light exposure, the number of lesions was decreased in the surviving cells, indicating DNA repair. Isolated mitochondria exposed to light generated singlet oxygen, superoxide anion, and the hydroxyl radical. Antioxidants confirmed the superoxide anion to be the primary species responsible for the mitochondrial DNA lesions. The effect of lipofuscin, a photoinducible intracellular generator of reactive oxygen intermediates, was investigated for comparison. Exposure of lipofuscin-containing cells to visible light caused an increase in both mitochondrial and nuclear DNA lesions compared with non-pigmented cells. We conclude that visible light can cause cell dysfunction through the action of reactive oxygen species on DNA and that this may contribute to cellular aging, age-related pathologies, and tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

“…Lipofuscin granules were isolated and purified from 50 -60-yearold human donors as described by Boulton et al (22), except that RPE cells were disrupted by mechanical homogenization instead of sonication. The concentration of the granules was determined using a hemocytometer.…”

Section: Lipofuscin Treatmentmentioning

confidence: 99%

Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells

Godley

Shamsi

Liang

et al. 2005

Journal of Biological Chemistry

Self Cite

385

294

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“…Meanwhile, lipofuscin similarly can generate superoxide anions after exposure to light with the rate of free radical production directly related to the intensity of light exposure and inversely related to the wavelength of light exposure. 80,[122][123][124][125] Generation of these free radicals can in turn cause RPE damage, induce lipid peroxidation, and lysosomal dysfunction. Studies on cultured cells by Davies et al 126 have shown these changes upon exposure to lipofuscin and low-wavelength light.…”

Section: Variables In Photochemical Injurymentioning

confidence: 99%

Retinal light toxicity

Youssef

Sheibani

Albert

2010

Eye

274

204

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The ability of light to enact damage on the neurosensory retina and underlying structures has been well understood for hundreds of years. While the eye has adapted several mechanisms to protect itself from such damage, certain exposures to light can still result in temporal or permanent damage. Both clinical observations and laboratory studies have enabled us to understand the various ways by which the eye can protect itself from such damage. Light or electromagnetic radiation can result in damage through photothermal, photomechanical, and photochemical mechanisms. The following review seeks to describe these various processes of injury and many of the variables, which can mitigate these modes of injury.

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“…Lipofuscin accumulates during life time in the RPE especially in ARMD. It leads to many damaging effects, including generation of ROS (Boulton et al, 1993) and phototoxicity (Davies et al, 2001). One specific lipofuscin fraction is A2E.…”

Section: Experimental Studies Regarding Light-induced Damage Of the Rmentioning

confidence: 99%

Oxidative Stress Induced Damage of the Human Retina: Overview of Mechanisms and Preventional Strategies

Engelmann¹,

Becker²,

Funk³

2012

Oxidative Stress - Environmental Induction and Dietary Antioxidants

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Lipofuscin is a photoinducible free radical generator

Cited by 190 publications

References 9 publications

Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells

Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells

Retinal light toxicity

Oxidative Stress Induced Damage of the Human Retina: Overview of Mechanisms and Preventional Strategies

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