Metallothionein-III Deficiency Exacerbates Light-Induced Retinal Degeneration

Tsuruma, Kazuhiro; Shimazaki, Hiroki; Ohno, Yuta; Inoue, Yuki; Honda, Akira; Imai, Shunsuke; Lee, Jin‐Yong; Shimazawa, Masamitsu; Satoh, Masahiko; Hara, Hideaki

doi:10.1167/iovs.12-10165

Cited by 16 publications

(13 citation statements)

References 42 publications

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“…MT is expressed in the tissues and central nervous system, and it has a high content of sulfhydryls, which targets it to scavenge superoxide anion and hydroxyl radicals with an affinity more than 300-fold higher that of reduced glutathione (48). In a previous report, Sod1, MT-II, and MT-III mRNAs were found to be increased in the retina 6 h after light exposure (28), and our data was consistent with this. However, astaxanthin did not influence Sod1, MT-II, and MT-III mRNA.…”

Section: Discussionsupporting

confidence: 92%

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The Protective Effects of a Dietary Carotenoid, Astaxanthin, Against Light-Induced Retinal Damage

et al. 2013

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Abstract. Dietary carotenoids exhibit various biological activities, including antioxidative activity. In particular, astaxanthin, a type of carotenoid, is well known as a powerful antioxidant. We investigated whether astaxanthin would protect against light-induced retinal damage. In an in vivo study, ddY male mice were exposed to white light at 8,000 lux for 3 h to induce retinal damage. Five days after light exposure, retinal damage was evaluated by measuring electroretinogram (ERG) amplitude and outer nuclear layer (ONL) thickness. Furthermore, expression of apoptotic cells, 8-hydroxy-deoxyguanosine (8-OHdG), was measured. In an in vitro study, retinal damage was induced by white light exposure at 2,500 lux for 24 h, and propidium iodide (PI)-positive cells was measured and intracellular reactive oxygen species (ROS) activity was examined. Astaxanthin at 100 mg/kg inhibited the retinal dysfunction in terms of ERG and ONL loss and reduced the expression of apoptotic and 8-OHdG-positive cells induced by light exposure. Furthermore, astaxanthin protected against increases of PI-positive cells and intracellular reactive oxygen species (ROS) activity in 661W cells. These findings suggest that astaxanthin has protective effects against light-induced retinal damage via the mechanism of its antioxidative effect.

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Section: Discussionsupporting

confidence: 92%

“…5, n = 10). We were referred to the previous report (28) to determine the timing of sampling retinas. The mRNA expression of Sod1, MT-II, and MT-III were elevated significantly after light exposure (20.7-, 1.7-, 1.2-fold increase, respectively).…”

Section: Expression Of Antioxidant Genesmentioning

confidence: 99%

The Protective Effects of a Dietary Carotenoid, Astaxanthin, Against Light-Induced Retinal Damage

et al. 2013

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“…ATO toxicity was evaluated by a Hoechst 33342/PI staining assay (Tsuruma et al, 2012). NB4 cells were seeded into 96-well plates at a density of 5 × 10 4 cells/mL in the medium (100 μL) of each well, incubated for 24 h with or without 5 μM CA, and then treated with ATO for 48 h. Following the addition of 100 μL PBS containing 2 μg/mL Hoechst 33342 and 2 μg/mL PI, the suspension was incubated at 37°C for 30 min in the dark.…”

Section: Fluorescent Cell Survival Assaymentioning

confidence: 99%

Nrf2 activation ameliorates cytotoxic effects of arsenic trioxide in acute promyelocytic leukemia cells through increased glutathione levels and arsenic efflux from cells

Nishimoto

Suzuki

Koike

et al. 2016

Toxicology and Applied Pharmacology

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“…Pigmented rodents tolerate light better than albino rodents 2 ; therefore, nonanesthetized mice were exposed for 3 hours to 8000 (ddY mice; albino) or 14,000 lux (C57BL/6J mice; pigmented) of white fluorescent light (Toshiba, Tokyo, Japan) in cages with reflective interiors, according to our previous report. 40 The ambient temperature during the exposure to light was maintained at 25 6 1.58C. After the exposure, all mice were placed in the dark for 24 hours and then returned to the previous light/dark cycle (see above).…”

Section: Exposure To Lightmentioning

confidence: 99%

Role of Heparin-Binding Epidermal Growth Factor–Like Growth Factor in Light-Induced Photoreceptor Degeneration in Mouse Retina

Inoue

Tsuruma²,

Nakanishi³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Inoue Y, Tsuruma K, Nakanishi T, et al. Role of heparin-binding epidermal growth factor-like growth factor in light-induced photoreceptor degeneration in mouse retina. Invest Ophthalmol Vis Sci. 2013;54:3815-3829. DOI:10.1167/iovs.12-11236 PURPOSE. Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been reported to have protective effects against various neuronal cell damage, its role in the retina has not been elucidated. Here, we investigated its role in light-induced photoreceptor degeneration using retinas and ventral forebrain-specific Hb-egf knockout (KO) mice.METHODS. Disruption of Hb-egf was confirmed by b-galactosidase (LacZ) staining and RT-PCR. Time-dependent changes in retinal HB-EGF were measured using quantitative RT-PCR and Western blotting. Retinal damage was induced by exposure to light. Recombinant human HB-EGF was injected intravitreally. Electroretinogram (ERG) and histological analyses were performed. To evaluate the effect of HB-EGF against light irradiation-induced cell death, 661W cells, a transformed mouse cone cell line, were used. RESULTS.LacZ-positive cells were observed and Hb-egf deletion was confirmed in the retinas of Hb-egf KO mice. Hb-egf and pro-HB-EGF levels were increased after light exposure in wildtype (WT) mice. Exposure to light reduced the a-and b-wave amplitudes of the dark-adapted ERG, and also outer nuclear layer (ONL) thickness, in Hb-egf KO mice versus WT mice. Treatment with HB-EGF improved both the a-and b-wave amplitudes and the thickness of the ONL. The 661W cell death induced by light irradiation was exacerbated by Hb-egf knockdown. HB-EGF also protected against light-induced cell death and reduced reactive oxygen species (ROS) production in 661W cells. HB-EGF treatment improved the a-wave amplitudes and the thickness of the ONL in Hb-egf KO mice.CONCLUSIONS. These data suggest that HB-EGF plays a pivotal role in light-induced photoreceptor degeneration. It therefore warrants investigation as a potential therapeutic target for such light-induced retinal diseases as age-related macular degeneration.

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Metallothionein-III Deficiency Exacerbates Light-Induced Retinal Degeneration

Cited by 16 publications

References 42 publications

The Protective Effects of a Dietary Carotenoid, Astaxanthin, Against Light-Induced Retinal Damage

The Protective Effects of a Dietary Carotenoid, Astaxanthin, Against Light-Induced Retinal Damage

Nrf2 activation ameliorates cytotoxic effects of arsenic trioxide in acute promyelocytic leukemia cells through increased glutathione levels and arsenic efflux from cells

Role of Heparin-Binding Epidermal Growth Factor–Like Growth Factor in Light-Induced Photoreceptor Degeneration in Mouse Retina

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