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Screening and evaluation of antioxidants for retinal pigment epithelial cell protection: L-ergothioneine as a novel therapeutic candidate through NRF2 activation.
Gu, Sijie; Wu, Siqi; Lin, Zesong; Han, Zhuo; Mo, Kunlun; Huang, Huaxing; Li, Mingsen; Li, Gen; Ouyang, Hong; Wang, Li.
Afiliação
  • Gu S; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Wu S; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Lin Z; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Han Z; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Mo K; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Huang H; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Li M; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Li G; Guangzhou Women and Children's Medical Center, Guangzhou, China.
  • Ouyang H; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
  • Wang L; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China. Electronic address: wangli59@mail.sysu.edu.cn.
Exp Eye Res ; 242: 109862, 2024 May.
Article em En | MEDLINE | ID: mdl-38490292
ABSTRACT
The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation. The inhibition of NRF2 abolished EGT's protective effects, suggesting that NRF2 activation contributes to its mechanism of action. In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Oxidativo / Ergotioneína / Fator 2 Relacionado a NF-E2 / Epitélio Pigmentado da Retina / Antioxidantes Limite: Animals / Humans Idioma: En Revista: Exp Eye Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Oxidativo / Ergotioneína / Fator 2 Relacionado a NF-E2 / Epitélio Pigmentado da Retina / Antioxidantes Limite: Animals / Humans Idioma: En Revista: Exp Eye Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China