Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina

Osada, Hideto; Okamoto, Takahiro; Kawashima, Hirohiko; Toda, Eriko; Miyake, Seiji; Nagai, Norihiro; Kobayashi, Saori; Ohta, Michio; Ozawa, Yoko

doi:10.1371/journal.pone.0178627

Cited by 42 publications

(47 citation statements)

References 54 publications

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“…Both of OS and ERS could finally induce cellular apoptosis. Antioxidants with the abilities of ameliorating the OS or ERS have been reported to reduce the light-induced damage on retinas [ 7 , 15 ]. The xanthophyll carotenoids—lutein, zeaxanthin and mesozeaxanthin (L/Zi) have higher concentration in visual system (eye and brain) compared to other carotenoids in the blood [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

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Lutein and Zeaxanthin Isomers Protect against Light-Induced Retinopathy via Decreasing Oxidative and Endoplasmic Reticulum Stress in BALB/cJ Mice

Yan

Beight

2018

Nutrients

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Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are the major factors underlying photoreceptor degeneration. Lutein, RR-zeaxanthin (3R,3’R-zeaxanthin) and RS (meso)-zeaxanthin (3R,3’S-RS- zeaxanthin) (L/Zi) could protect against cell damage by ameliorating OS in retina. In this study, we examined the effect of L/Zi supplementation in a mouse model of photoreceptor degeneration and investigated whether the treatment of L/Zi ameliorated OS and ERS. BALB/cJ mice after light exposure were used as the animal model. The protective effects of L/Zi were observed by electroretinography (ERG) and terminal deoxyuridine triphosphate nick-end labeling (TUNEL) analysis. The underlying mechanisms related to OS and ERS were explored by Western blotting. After L/Zi treatment, the ERG amplitudes were significantly higher, and the number of TUNEL-positive cells was significantly reduced compared to that of the vehicle group. Western blotting results revealed that OS was ameliorated according to the significant downregulation of phosphorylated c-Jun N-terminal kinase (p-JNK), and significant upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, ERS was reduced according to the significant downregulation of 78 kDa glucose-regulated protein (GRP78), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF4) and activating transcription factor (ATF6). Our data shows that L/Zi provided functional and morphological preservation of photoreceptors against light damage, which is probably related to its mitigation of oxidative and endoplasmic reticulum stress.

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Section: Discussionmentioning

confidence: 99%

“…During light exposure, the production of reactive oxygen species (ROS) is increased which causes retinal degeneration [ 6 ]. Quite a few antioxidants have been confirmed to be effective in reducing photoreceptor degeneration in animal models of light-induced damage [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Lutein and Zeaxanthin Isomers Protect against Light-Induced Retinopathy via Decreasing Oxidative and Endoplasmic Reticulum Stress in BALB/cJ Mice

Yan

Beight

2018

Nutrients

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“…The Light-induced retinal degeneration experiments were performed as described previously. 31 In brief, before light exposure, mice were dark-adapted by maintaining them in complete darkness for 12 h. Then, pupils were dilated with a mixture of 0.5% tropicamide and 0.5% phenylephrine (Mydrin-P; Santen Pharmaceutical, Osaka, Japan) just before exposure to the light. We used 10,000 lux (WT and SIRT3 KO mice with B6 background) or 13,000 lux (WT and SIRT3 KO mice with 129 background) from a white fluorescence lamp for 3 h (WT and SIRT3 KO mice with B6 background) or 4 h (WT and SIRT3 KO mice with 129 background) in a dedicated exposure box.…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective role of retinal SIRT3 against acute photo-stress

et al. 2017

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SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice. We demonstrate that SIRT3 deficiency causes acute reactive oxygen species accumulation and endoplasmic reticulum stress in the retina after the light exposure, which leads to increased photoreceptor death, retinal thinning, and decreased retinal function. Using a photoreceptor-derived cell line, we revealed that reactive oxygen species were the upstream initiators of endoplasmic reticulum stress. Under SIRT3 knockdown condition, we demonstrated that decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These studies have helped to elucidate the critical role of SIRT3 in photoreceptor neuronal survival, and suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders.

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“…Recently, the retinal protective effects against light damage of oral bilberry extract (containing about 39% anthocyanin) [ 17 ] and epigallocatechin gallate [ 18 ] have been reported. However, in those experiments, bilberry extract and epigallocatechin gallate were administered at doses of 750 mg/kg and 400 mg/kg BW, respectively.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

Ishihara

Kaidzu

Kimura³

et al. 2018

Nutrients

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Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

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Neuroprotective effect of bilberry extract in a murine model of photo-stressed retina

Cited by 42 publications

References 54 publications

Lutein and Zeaxanthin Isomers Protect against Light-Induced Retinopathy via Decreasing Oxidative and Endoplasmic Reticulum Stress in BALB/cJ Mice

Lutein and Zeaxanthin Isomers Protect against Light-Induced Retinopathy via Decreasing Oxidative and Endoplasmic Reticulum Stress in BALB/cJ Mice

Neuroprotective role of retinal SIRT3 against acute photo-stress

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

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