Photochemical studies of A2-E

Cantrell, Ann; McGarvey, David J.; Roberts, Joan E.; Sarna, Tadeusz; Truscott, T. George

doi:10.1016/s1011-1344(01)00224-x

Cited by 32 publications

(37 citation statements)

References 9 publications

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“…Recently, we reported a detailed comparison of the action spectra for oxygen photoconsumption by LF and A2E and therein clearly demonstrated that A2E is not responsible for the photouptake of oxygen by LF (36). This conclusion is also supported by recent detailed studies quantifying A2E's inefficient photoproduction of various reactive oxygen intermediates (28,30,31,40). Collectively, these results establish that A2E is not the dominant photoreactive component of LF.…”

supporting

confidence: 72%

Spectroscopic and morphological studies of human retinal lipofuscin granules

Haralampus-Grynaviski

Lamb²,

Clancy³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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The emission properties of ocular lipofuscin granules isolated from human retinal pigment epithelial cells are examined by using steady-state fluorescence spectroscopy and spectrally resolved confocal microscopy. The shape of the emission spectrum of a thick sample of lipofuscin granules dried on glass varies with excitation energy. The polarization of this emission is wavelength-dependent, exhibiting significant polarization near the excitation wavelength and becoming mostly depolarized over the majority of the emission spectrum. These results show that the yellow-emitting fluorophores [e.g., A2E (2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium)] are excited as a result of energy transfer within the granules and therefore are not the dominant blue-absorbing chromophores within lipofuscin granules. Atomic force microscopy images show lipofuscin granules to be an aggregated structure. Bulk and in vivo emission measurements must therefore take into account the effect of Raleigh scattering. When corrected for scattering, the emission spectrum of a thick lipofuscin deposit or intracellular lipofuscin resembles that for A2E. The sum of the emission spectra of a collection of individual granules also resembles the emission spectrum of A2E, but the spectrum of individual granules varies significantly. This result suggests that the agreement between the emission spectra of lipofuscin and A2E is fortuitous, and the collective data indicate the presence of several blue-absorbing chromophores in lipofuscin and show A2E is not the dominant yellow-emitting fluorophore in many of the granules studied.L ipofuscin (LF) is a common morphological result of the aging process and is manifested as a heterogeneous complex of fluorescent, lipid-protein aggregates found in the cytoplasm of postmitotic cells (1-5). In the retinal pigment epithelium (RPE) of the human eye, the formation of LF is attributed to the accumulation of indigestible end-products from the phagocytosis of photoreceptor outer segments (1, 6-8). LF accumulates in RPE cells as clusters of granules and can occupy Ϸ20% of the cytoplasmic space by 80 yr of age (9). LF exhibits a yellow fluorescence ( max Ϸ 600 nm) upon blue-light excitation (10). In vitro experiments also show that blue-light excitation of cultured RPE cells ʈ fed LF generates a variety of reactive oxygen intermediates (including hydrogen peroxide, singlet oxygen, and superoxide radical anion), which renders LF phototoxic to cultured RPE cells (11)(12)(13).Determining the molecule(s) responsible for the aerobic photoreactivity and emissive properties of LF is the focus of current research. In a groundbreaking paper in 1988, Eldred and Katz (14) analyzed chloroform:methanol (2:1, vol͞vol) extracts of RPE cells and separated several emissive bands by using TLC. A variety of yellow-emitting fluorophores were found. To date, only two isomers of a pyridinium bis-retinoid, A...

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supporting

confidence: 72%

Spectroscopic and morphological studies of human retinal lipofuscin granules

Haralampus-Grynaviski

Lamb²,

Clancy³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…The photodamage observed in RPE cells is oxygen-dependent and is diminished by antioxidants, which suggests that the blue light effect is associated with oxidative stress (Wielgus et al 2010). Although dimerized vitamin A may photogenerate a little amount of reactive oxygen species (Cantrell et al 2001), the formation of oxidation products is highly toxic to RPE cells (Wielgus et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Supplementation of procyanidins B2 attenuates photooxidation-induced apoptosis in ARPE-19 cells

Jiang

Sun

et al. 2016

International Journal of Food Sciences and Nutrition

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During the aging process, dimers of dietary vitamin A accumulated in retinal pigment epithelium (RPE) cells. Vitamin A dimer-mediated photooxidation resulted in RPE apoptosis, which is associated with age-related degenerative disease of retina, leading to blindness. It has been reported that proanthocyanidin-rich grape seed extract reduces oxidative stress in the eye. In this study, we investigated the underlying mechanism of photooxidation-induced apoptosis inhibition by procyanidins B2 (PB2), one of the main components of grape seed proanthocyanidin. To mimic vitamin A dimer-mediated photooxidation, ARPE-19 cells that accumulated vitamin A dimer, A2E, were used as a model system. Exposure of A2E loaded ARPE-19 cells to blue light induced ER stress and resulted in significant apoptosis. Pretreatment of blue light-exposed A2E containing ARPE-19 cells with PB2 inhibited apoptosis, increased the ratio of Bcl-2/Bax in the mitochondria, attenuated ROS and cytochrome c release, and decreased caspase cleavage. Additionally, PB2 inhibited the phosphorylation of ER stress markers elF2α and IRE1α and reduced CHOP expression. Moreover, PB2 inhibition of apoptosis is dependent on the UPR chaperone GRP78, indicating PB2 inhibits vitamin A dimer-mediated apoptosis in RPE cells by activating the UPR.

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“…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). Measurements of the quantum yield of singlet-oxygen generation by A2E or quantum yields of intersystem crossing of A2E indicate relatively modest singletoxygen production when measured in polar solvents and when compared to the performance of photosensitizers used in photodynamic therapy.…”

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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Photochemical studies of A2-E

Cited by 32 publications

References 9 publications

Spectroscopic and morphological studies of human retinal lipofuscin granules

Spectroscopic and morphological studies of human retinal lipofuscin granules

Supplementation of procyanidins B2 attenuates photooxidation-induced apoptosis in ARPE-19 cells

Mechanisms involved in A2E oxidation

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