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Wolfberry-derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways.

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机构: [1]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China. [2]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. [3]The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. [4]The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China. [5]Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China. [6]Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, China. [7]Co-Innovation Center of Neuroregeneration, Nantong University, Jiangsu, China. [8]Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
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关键词: anti-inflammation MAPK pathway photoreceptor degeneration STAT3 wolfberry

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Retinitis pigmentosa (RP) is a group of inherited photoreceptor degeneration diseases that causes blindness without effective treatment. The pathogenesis of retinal degeneration involves mainly oxidative stress and inflammatory responses. Zeaxanthin dipalmitate (ZD), a wolfberry-derived carotenoid, has anti-inflammatory and anti-oxidative stress effects. Here we investigated whether these properties of ZD can delay the retinal degeneration in rd10 mice, a model of RP, and explored its underlying mechanism. One shot of ZD or control vehicle was intravitreally injected into rd10 mice on postnatal day 16 (P16). Retinal function and structure of rd10 mice were assessed at P25, when rods degenerate substantially, using a visual behavior test, multi-electrode-array recordings and immunostaining. Retinal pathogenic gene expression and regulation of signaling pathways by ZD were explored using transcriptome sequencing and western blotting. Our results showed that ZD treatment improved the visual behavior of rd10 mice and delayed the degeneration of retinal photoreceptors. It also improved the light responses of photoreceptors, bipolar cells and retinal ganglion cells. The expression of genes that are involved in inflammation, apoptosis and oxidative stress were up-regulated in rd10 mice, and were reduced by ZD. ZD further reduced the activation of two key factors, signal transducer and activator of transcription 3 and chemokine (C-C motif) ligand 2, down-regulated the expression of the inflammatory factor GFAP, and inhibited extracellular signal regulated protein kinases and P38, but not the JNK pathways. In conclusion, ZD delays the degeneration of the rd10 retina both morphologically and functionally. Its anti-inflammatory function is mediated primarily through the signal transducer and activator of transcription 3, chemokine (C-C motif) ligand 2 and MAPK pathways. Thus, ZD may serve as a potential clinical candidate to treat RP.© 2021 International Society for Neurochemistry.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 生化与分子生物学 2 区 神经科学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 生化与分子生物学 3 区 神经科学
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出版当年[2019]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 NEUROSCIENCES
最新[2023]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 NEUROSCIENCES

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China. [2]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
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通讯机构: [1]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China. [7]Co-Innovation Center of Neuroregeneration, Nantong University, Jiangsu, China. [8]Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA. [*1]Guangdong-Hongkong- Macau Institute of CNS Regeneration, Jinan University, 601 West Huangpu Ave, Guangzhou 510632, Guangdong, China
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