著者

Wataru Otsu Hideaki Hara Kenjiro Ogawa

出版者

Japanese Society for Food Science and Technology

雑誌

Food Science and Technology Research (ISSN:13446606)

巻号頁・発行日

pp.FSTR-D-23-00032, (Released:2023-06-19)

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Retinal pigment epithelium (RPE) is an essential vision component of the human eye due to its nutritional and functional support to photoreceptors. Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease characterized by RPE loss. Ultraviolet (UV) light exposure induces injurious effects on human eyes by generating excess reactive oxygen species (ROS) and is responsible for photoaging. Bilberry (Vaccinium myrtillus L.) and its extract (VME) are known for their potent antioxidant properties. In the present study, we examined the effect of VME on UVA-induced RPE injury. Using an in vitro system with human RPE (ARPE-19) cells, pretreatment with VME suppressed cell death, mitochondrial superoxide production, and activation of the stress response that occurs following UVA irradiation. Furthermore, VME attenuated rotenone-induced mitochondrial ROS and concomitant reduction in cell viability. Our findings suggest that VME has a protective effect against UVA-induced RPE cell damage.

著者

Kenjirou Ogawa Takara Karitani Wataru Otsu Kazuo Nishiyama Hisato Kunitake Yo Goto Shota Nomiyama Hideaki Hara Masao Yamasaki

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.6, no.3, pp.87-97, 2023 (Released:2023-05-26)

参考文献数

29

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Background: Blue light causes retinal photoreceptor damage via oxidative and endoplasmic reticulum (ER) stress. A previous study showed that blueberry stem extract (BStEx) and its active components have cytoprotective effects against blue-light-induced photoreceptor cell damage by suppressing oxidative stress. This study demonstrated the inhibitory effect of BStEx against blue light-induced ER stress in photoreceptor cells. Methods: The photoreceptor cells treated with BStEx or the antioxidant N-Acetyl-L-cysteine (NAC) as a positive control were used and then exposed to blue light. The cytoprotective effects of BStEx and NAC were evaluated using CCK-8. The ER stress-related protein expression changes over time, and its levels were measured after each exposure time to blue light in photoreceptor cells treated with BStEx or NAC. Results: BStEx and NAC showed protective effects against blue-light-induced photoreceptor morphological abnormalities and cell damage. Although blue light triggered ER stress factors such as BiP, PERK, ATF6, eIF2α, ATF4, and CHOP, which in turn stimulated cell cycle arrest factors p53 and p21 and upregulation of apoptosis-inducing factors caspase-3. However, BStEx suppressed the increase in expression of BiP, ATF4, ATF6, CHOP, p53, p21, and caspase-3, but not mitochondrial apoptotic factors Bax and cytochrome c. Furthermore, the antioxidant NAC showed similar suppressive effects on BStEx. Conclusion: Our findings suggest that blue light-induced ER stress is primarily caused by oxidative stress, and BStEx might suppress ER stress via an antioxidant effect. The antioxidant NAC contributes to the cell proliferative capacity and suppression of apoptosis in photoreceptor cells.

著者

Kodai Ishida Tomohiro Yako Miruto Tanaka Wataru Otsu Shinsuke Nakamura Masamitsu Shimazawa Hideshi Tsusaki Hideaki Hara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.7, pp.937-946, 2021-07-01 (Released:2021-07-01)

参考文献数

45

被引用文献数

4

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The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for eye diseases. Photokeratitis is damage to the corneal epithelium resulting in a painful eye condition caused by unprotected exposure to UV rays, usually from sunlight, and is often found in people who spend a long time outdoors. In modern life, human eyes are exposed to artificial light from light-emitting diode (LED) displays of computers and smartphones, and it has been shown that short-wavelength (blue) LED light can damage eyes, especially photoreceptors. However, the effect of blue LED light on the cornea is less understood. In addition, it is important to develop new treatments for preserving human eyesight and eye health from light stress. Here, we used human corneal epithelial cells-transformed (HCE-T) cells as an in-vitro model to investigate the protective effect of NSP-116, an imidazolyl aniline derivative, against the oxidative stress induced by light in the corneal epithelium. Treatment with 10 µM NSP-116 significantly increased the cell viability and reduced the death ratio following UV or blue LED light exposure. Furthermore, NSP-116 treatment decreased light-induced reactive oxygen species production and preserved the mitochondrial membrane potential. Immunoblotting data showed that NSP-116 suppressed the stress response pathway. Finally, NSP-116 treatment prevented corneal epithelial apoptosis induced by blue LED light in an in-vivo mouse model. In conclusion, NSP-116 has a protective effect against oxidative stress and corneal cell death from both UV and blue LED light exposure.

著者

Yuichi Saito Hiroyuki Okuyoshi Shinsuke Nakamura Wataru Otsu Akihiro Yamaguchi Peter F. Hitchcock Mikiko Nagashima Masamitsu Shimazawa Hideaki Hara

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.3, no.3, pp.92-96, 2020 (Released:2020-11-26)

参考文献数

37

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Regenerative medicine aims to replenish damaged tissue. Boosting the capacity of intrinsic stem cells to proliferate is one key for successful regeneration. Adult zebrafish possess tissue resident stem and progenitor cells, which contribute to homeostatic growth and tissue regeneration. In the intact retina, Müller glia sporadically divide to generate fate restricted, proliferative precursors. Cell death reprograms Müller glia into stem cells that divide and produce multi-potent retinal progenitors. Using zebrafish, we evaluated the effect of taurine-conjugated bile acid, Tauroursodeoxycholic acid (TUDCA) on retinal regeneration. In the intact retina, treatment with TUDCA significantly promotes proliferation of the fate restricted precursors, but has no effect on Müller glia. Following constant light exposure, TUDCA attenuates photoreceptor death, indicating that TUDCA is neuroprotective. Following a stab wound, which initiates death of retinal neurons and reprogramming of Müller glia, treatment with TUDCA significantly increases the number of proliferating cells. In the intact retina, TUDCA-induced proliferation was accompanied by decreased expression of cell cycle inhibitors. These results suggest that TUDCA promotes proliferation of actively-cycling stem and progenitors, identifying TUDCA as a potential reagent to promote regeneration of retinal neurons.