BMC Ophthalmology
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2020
·Vol. 20
·期 1
·1-10
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IF 1.413
Yan Weiming,Long Pan,Wei Dongyu,Yan Weihua,Zheng Xiangrong,Chen Guocang,Wang Jiancong,Zhang Zuoming,Chen Tao,Chen Meizhu
Background Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats.Methods Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted.Results Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein.Conclusion sTogether, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.
研究领域:
眼科学
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药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
·
IF 7.5
Yijing Yang,Ying Wang,Ying Deng,Jing Lu,Li Xiao,Jie Li,Yasha Zhou,Fujiao Nie,Xiangdong Chen,Jun Peng,Hanyu Tan,Yuhui Qin,Qinghua Peng
Aim of the study To assess the impact of Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) on retinitis pigmentosa (RP) and to explore the mechanisms by which FSE can prevent oxidative stress-induced photoreceptor ferroptosis in RP. Methods Hydrogen peroxide(H 2 O 2 ) was used to induce oxidative stress in 661 W cells, which were then examined using flow cytometry and enzyme linked immunosorbent assay (ELISA). Changes in mitochondria were observed by using an electron microscope to characterize the ferroptosis of the cells. The protective effect of FSE on the retina function and structure of rd10 mice was evaluated using histopathological examination, fundus photographs, and electroretinography (ERG). Protein expression levels of Tumor Protein p53 (P53), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione peroxidase 4 (GPX4), Arachidonate-12-Lipoxygenase (ALOX12), and Dipeptidyl peptidase 4 (DPP4) were evaluated by Western blot assays in Vivo and in Vitro. Results H 2 O 2 -induced 661 W cells increased oxidative stress products and P53 and ALOX12, decreasing the expression of SLC7A11, GPX4, and DPP4. GPX4 activator does not reduce reactive oxygen species (ROS) generation and has little effect on ferroptosis. Fer-1 and FSE attenuate ROS generation and inhibit ferroptosis of photoreceptors in RP via inhibited P53 expression and increased SLC7A11 and GPX4 expression. Conclusion FSE may be available in clinical therapeutics to alleviating RP and the mechanism by which inhibits ferroptosis of photoreceptors following oxidative stress via the P53/ SLC7A11 pathway.
研究领域:
眼科学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
·
IF 7.9
Yulin Qi,Lu Liu,Dan Liang,Shiyun Tang,Xiaoyi Yu,Hejiang Ye,Nianzhi Chen
Background Retinitis pigmentosa (RP) refers to a group of progressive photoreceptor degenerative diseases . The activation of microglia has been reported to play an important role in the photoreceptor degeneration in RP retinal. Bujing Yishi tablets (BJYS), a Chinese herbal medicine , has been used to treat retinal diseases in China with desirable effect in improving visual function. However, the mechanisms underlying the efficacy of BJYS treatment in RP are not yet fully understood. Purpose Based on the preliminary experiments, this study aimed to investigate the therapeutic mechanism involved in treating N -Methyl- N -Nitrosourea (MNU)-induced retinal degeneration of RP with BJYS. Methods To explore the efficacy of BJYS, a rat experimental RP model was established through intraperitoneal injection of MNU (50 mg/kg). Two experiment was carried out. After the treatment, we conducted H&E, TUNEL , retinal cytokine levels and IBA-1 expression in microglia to confirm the impact on RP model. The specific mechanism of action of BJYS tablet was assessed by western blot , real-time polymerase chain reaction (RT-PCR), and immunofluorescence to determine the mRNA and protein expression levels involved in clarifying the effectiveness of BJYS exerted through P2X7R/CX3CL1/CX3CR1 pathway. Results Significant alleviation of retinal morphological structure and photoreceptor degeneration by BJYS treatment was observed in the retinal of MNU-induced RP rats, BJYS prevented the reduction of ONL thickness and decreased the level of apoptotic cells in ONL. It also inhibited microglia overactivation and reduced retinal levels of IL-1β, IL-6, TNF-α. In addition, BJYS decreased the protein expression and mRNA expression of P2X7, CX3CL1 and CX3CR1 and reduced the phosphorylation of p38 MAPK . Conclusion In summary, this study suggested that BJYS treatment could alleviate photoreceptors degeneration of RP by inhibiting microglia overactivation and inflammation through the P2X7R/CX3CL1/CX3CR1 pathway. These effects suggest that BJYS tablets may serve as a promising oral therapeutic agent for RP.
研究领域:
眼科学
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药理学
·
神经科学
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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