Blue Light-Induced Singlet Oxygen Generation by Retinal Lipofuscin in Non-Polar Media

Różanowska, Malgorzata Barbara; Wessels, Jurina M.; Boulton, Mike; Burke, Janice M.; Rodgers, Michael A. J.; Truscott, T. G.; Sarna, Tadeusz

doi:10.1016/s0891-5849(97)00395-x

Cited by 213 publications

(182 citation statements)

References 12 publications

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“…Uptake of oxygen has been measured in both suspensions of RPE cells and in lipofuscin granules with efficiency being greatest using short-wavelength visible light (Pawlak et al, 2002;Rozanowska et al, 1995;Rozanowska et al, 2002;Rozanowska et al, 2004). It is reported that photoexcited pigments in lipofuscin granules form triplet states with both singlet oxygen and superoxide anion being produced (Gaillard et al, 1995;Reszka et al, 1995;Rozanowska et al, 1995;Rozanowska et al, 1998). Using ESR (electron spin resonance) with DMPO as a spin trapping agent, superoxide anion production by irradiated A2E has previously been detected (Pawlak et al, 2002) while photosensitization studies have shown that photoexcitation of A2E also leads to singlet oxygen production Cantrell et al, 2001;Kanofsky et al, 2003;Lamb et al, 2001;Pawlak et al, 2003;Ragauskaite et al, 2001;Reszka et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms involved in A2E oxidation

Kim

Jockusch

Itagaki

et al. 2008

Experimental Eye Research

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A2E is one of the bis-retinoid pyridinium compounds that accumulate as lipofuscin pigments in retinal pigment epithelial (RPE) cells in association with aging and in some inherited forms of retinal degeneration. Here we observed that 430 nm irradiation of A2E in the presence of the spin trap DMPO, led to the appearance of a superoxide dismutase-inhibitable electron paramagnetic resonance (EPR) spectrum characteristic of DMPO-OH; this finding was indicative of hydroxyl radical (OH) formation following initial spin trapping of superoxide anion by DMPO. We also observed an increase in dihydroethidium (HEt) fluorescence and luminol-based chemiluminescence that on the basis of inhibition by superoxide dismutase, was indicative of superoxide anion generation when A2E was irradiated at 430 nm in cell-free systems. Nevertheless, while A2E was readily oxidized in the presence of a singlet oxygen generator, superoxide anion did not serve to oxidize A2E. Specifically, by HPLC quantitation and FAB-mass spectroscopy, there was no evidence of A2E oxidation when A2E was incubated with a superoxide anion generator (xanthine/xanthine oxidase) in a variety of solvents (100% PBS, 30% DMSO in PBS, 100% MeOH and CHCl 3 ) or in the presence of detergent. On the other hand, however, peroxy-A2E, an oxidized form of A2E with an endoperoxide moiety on the short-arm of the molecule, readily underwent further oxygen addition when incubated with xanthine/xanthine oxidase. Superoxide anion may be generated by irradiation of A2E but is not involved in the early events that oxidize A2E. Superoxide can contribute to the further oxidation of already-oxidized A2E.

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Section: Discussionmentioning

confidence: 99%

Mechanisms involved in A2E oxidation

Kim

Jockusch

Itagaki

et al. 2008

Experimental Eye Research

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“…180 Further study has revealed that the lipofuscinmediated generation of ROIs in response to irradiation is wavelength-dependent, being greatest for the blue region of the visible spectrum. 181 This photoinducible free radical generation by lipofuscin has been shown to result in lipid peroxidation and enzyme inactivation, 216 as well as RPE cellular dysfunction. 47 A2-E is a lysosomotropic agent that has the capacity to compromise both lysosomal function and integrity.…”

Section: Lipofuscinmentioning

confidence: 99%

The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration

Beatty

Koh²,

Phil

et al. 2000

Survey of Ophthalmology

1,772

1,347

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Abstract. Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although a protective effect of high plasma concentrations of ␣ -tocopherol has been convincingly demonstrated. Macular pigment is also believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color, and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated. Age-related macular degeneration (AMD) is the leading cause of blind registration in the western world, 119 and its prevalence is likely to rise as a consequence of increasing longevity. 225 There is a general consensus that cumulative oxidative damage is responsible for aging, and may, therefore, play an important role in the pathogenesis of AMD. In this article, we review the literature germane to oxidative processes in the retina and examine the evidence for a causal link between oxidative stress and age-related macular degeneration.

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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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Blue Light-Induced Singlet Oxygen Generation by Retinal Lipofuscin in Non-Polar Media

Cited by 213 publications

References 12 publications

Mechanisms involved in A2E oxidation

Mechanisms involved in A2E oxidation

The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration

Retinal light toxicity

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