Ucf-101 alleviates Ischaemia/Reperfusion induced retinal inflammation and injury via suppressing oxidative damage.

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2024-08-01 Epub Date: 2024-06-15 DOI:10.1007/s10735-024-10213-5

Yuan-Jun Qin, Guangyi Huang, Jing Liao, Li Jiang, Fen Tang, Ningning Tang, Yiyi Hong, Chaolan Shen, Qianqian Lan, Fan Xu, Lifei Chen

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引用次数: 0

Abstract

The Omi/HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryliodine]-1,3-diphenyl-2-thiobarbituric acid (Ucf-101) has shown neuroprotective effects in the central nervous system. However, whether Ucf-101 can protect retinal ganglion cells (RGCs) after retinal ischemia/reperfusion (IR) has not been investigated. We aimed to investigate the effects of Ucf-101 on RGCs apoptosis and inflammation after IR-induced retinal injury in mice. We injected Ucf-101 into the mouse vitreous body immediately after IR injury. After 7 days, hematoxylin and eosin staining was conducted to assess retinal tissue damage. Next, retrograde labeling with FluoroGold, counting of RGCs and TUNEL staining were conducted to evaluate apoptosis. Immunohistochemistry, immunofluorescence staining, and western blotting were conducted to analyze protein levels. IR injury-induced retinal tissue damage could be prevented by Ucf-101 treatment. The number of TUNEL-positive RGCs was reduced by Ucf-101 treatment in mice with IR injury. Ucf-101 treatment inhibited the upregulation of Bax, cleaved caspase-3 and cleaved caspase-9 and activated the JNK/ERK/P38 signaling pathway. Furthermore, Ucf-101 treatment inhibited the upregulation of glial fibrillary acidic protein (GFAP), vimentin, Iba1 and CD68 in mice with IR injury. Ucf-101 prevents retinal tissue damage, improves the survival of RGCs, and suppresses microglial overactivation after IR injury. Ucf-101 might be a potential target to prevent RGCs apoptosis and inflammation in neurodegenerative eye diseases.

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Ucf-101 可通过抑制氧化损伤减轻缺血/再灌注诱导的视网膜炎症和损伤。

Omi/HtrA2抑制剂5-[5-（2-硝基苯基）呋喃碘]-1,3-二苯基-2-硫代巴比妥酸（Ucf-101）对中枢神经系统具有神经保护作用。然而，Ucf-101 是否能在视网膜缺血/再灌注（IR）后保护视网膜神经节细胞（RGCs）尚未得到研究。我们的目的是研究 Ucf-101 对 IR 引起的小鼠视网膜损伤后 RGCs 凋亡和炎症的影响。我们在红外损伤后立即将 Ucf-101 注入小鼠玻璃体内。7 天后，进行苏木精和伊红染色以评估视网膜组织损伤。接着，用 FluoroGold 进行逆行标记、计数 RGCs 和 TUNEL 染色，以评估细胞凋亡情况。免疫组化、免疫荧光染色和免疫印迹法分析蛋白质水平。Ucf-101 可以阻止红外损伤引起的视网膜组织损伤。Ucf-101治疗可减少红外损伤小鼠TUNEL阳性RGC的数量。Ucf-101 可抑制 Bax、裂解的 caspase-3 和裂解的 caspase-9 的上调，并激活 JNK/ERK/P38 信号通路。此外，Ucf-101 还能抑制红外损伤小鼠神经胶质纤维酸性蛋白（GFAP）、波形蛋白、Iba1 和 CD68 的上调。Ucf-101 可防止视网膜组织损伤，提高 RGC 的存活率，抑制红外损伤后小胶质细胞的过度激活。Ucf-101可能是防止神经退行性眼病中RGCs凋亡和炎症的潜在靶点。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.