Neuroprotection of Rodent and Human Retinal Ganglion Cells In Vitro/Ex Vivo by the Hybrid Small Molecule SA-2.
Neuroprotection of Rodent and Human Retinal Ganglion Cells In Vitro/Ex Vivo by the Hybrid Small Molecule SA-2.
复制标题
杂合小分子SA-2对啮齿动物和人视网膜神经节细胞的神经保护作用
DOI：
10.3390/cells11233741
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发表时间：
2022-11-23
期刊：
影响因子：
6
通讯作者：
Stankowska, Dorota L.
中科院分区：
文献类型：
--
作者：
Pham, Jennifer H.;Johnson, Gretchen A.;Rangan, Rajiv S.;Amankwa, Charles E.;Acharya, Suchismita;Stankowska, Dorota L.
关键词：
评价了杂合抗氧化剂-一氧化氮供体化合物SA-2在视网膜神经节细胞（RGC）变性模型中的神经保护作用的潜在机制。在体外营养因子（TF）剥夺模型在原代大鼠视网膜节细胞和离体人视网膜外植体被用来模拟青光眼神经变性。在用媒介物或SA-2处理后评估细胞存活。在单独的实验中，叔丁基过氧化氢（TBHP）和内皮素-3（ET-3）分别用于离体大鼠视网膜外植体和原代大鼠RGCs，以诱导氧化损伤。治疗后评估线粒体和细胞内活性氧（ROS）。在TF剥夺模型中，SA-2处理在原代RGC中产生凋亡和死细胞计数的显著减少，并且在离体人视网膜外植体中产生RGC存活的显著增加。在氧化应激诱导的模型中，与媒介物处理组相比，在SA-2处理组中观察到ROS产生的显著减少。化合物SA-2通过减少细胞凋亡和降低ROS水平对大鼠和人RGC中的各种脑损伤具有神经保护作用。SA-2对线粒体和细胞氧化应激的改善可能是一种潜在的治疗策略，用于预防青光眼RGCs的神经变性。
The mechanisms underlying the neuroprotective effects of the hybrid antioxidant-nitric oxide donating compound SA-2 in retinal ganglion cell (RGC) degeneration models were evaluated. The in vitro trophic factor (TF) deprivation model in primary rat RGCs and ex vivo human retinal explants were used to mimic glaucomatous neurodegeneration. Cell survival was assessed after treatment with vehicle or SA-2. In separate experiments, tert-Butyl hydroperoxide (TBHP) and endothelin-3 (ET-3) were used in ex vivo rat retinal explants and primary rat RGCs, respectively, to induce oxidative damage. Mitochondrial and intracellular reactive oxygen species (ROS) were assessed following treatments. In the TF deprivation model, SA-2 treatment produced a significant decrease in apoptotic and dead cell counts in primary RGCs and a significant increase in RGC survival in ex vivo human retinal explants. In the oxidative stress-induced models, a significant decrease in the production of ROS was observed in the SA-2-treated group compared to the vehicle-treated group. Compound SA-2 was neuroprotective against various glaucomatous insults in the rat and human RGCs by reducing apoptosis and decreasing ROS levels. Amelioration of mitochondrial and cellular oxidative stress by SA-2 may be a potential therapeutic strategy for preventing neurodegeneration in glaucomatous RGCs.
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影响因子：
3.7
作者：
Minton AZ;Phatak NR;Stankowska DL;He S;Ma HY;Mueller BH;Jiang M;Luedtke R;Yang S;Brownlee C;Krishnamoorthy RR
通讯作者：
Krishnamoorthy RR
影响因子：
2
作者：
Kashiwagi, K;Iizuka, Y;Tsukahara, S
通讯作者：
Tsukahara, S
糖尿病小鼠肾传入小动脉活性氧和内皮素-1 收缩性的增强与典型 Wnt 信号转导相关
影响因子：
2.8
作者：
Zhang S;Huang Q;Wang Q;Wang Q;Cao X;Zhao L;Xu N;Zhuge Z;Mao J;Fu X;Liu R;Wilcox CS;Patzak A;Li L;Lai EY
通讯作者：
Lai EY
DOI：
10.3390/antiox9111031
发表时间：
2020-10-22
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Garcia-Medina JJ;Rubio-Velazquez E;Lopez-Bernal MD;Cobo-Martinez A;Zanon-Moreno V;Pinazo-Duran MD;Del-Rio-Vellosillo M
通讯作者：
Del-Rio-Vellosillo M
影响因子：
4.4
作者：
Lieven, CJ;Hoegger, MJ;Levin, LA
通讯作者：
Levin, LA