North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Cells. 2024 Feb 25;13(5):396. doi: 10.3390/cells13050396.
Embolism, hyperglycemia, high intraocular pressure-induced increased reactive oxygen species (ROS) production, and microglial activation result in endothelial/retinal ganglion cell death. Here, we conducted in vitro and in vivo ischemia/reperfusion (I/R) efficacy studies of a hybrid antioxidant-nitric oxide donor small molecule, to assess its therapeutic potential for ocular stroke.
To induce I/R injury and inflammation, we subjected R28 and primary microglial cells to oxygen glucose deprivation (OGD) for 6 h in vitro or treated these cells with a cocktail of TNF-α, IL-1β and IFN-γ for 1 h, followed by the addition of (10 µM). Inhibition of microglial activation, ROS scavenging, cytoprotective and anti-inflammatory activities were measured. In vivo I/R-injured mouse retinas were treated with either PBS or (2%) intravitreally, and pattern electroretinogram (ERG), spectral-domain optical coherence tomography, flash ERG and retinal immunocytochemistry were performed.
significantly inhibited microglial activation and inflammation in vitro. Compared to the control, the compound significantly attenuated cell death in both microglia (43% vs. 13%) and R28 cells (52% vs. 17%), decreased ROS (38% vs. 68%) production in retinal microglia cells, preserved neural retinal function and increased SOD1 in mouse eyes.
is protective to retinal neurons by decreasing oxidative stress and inflammatory cytokines.
栓塞、高血糖、高眼压引起的活性氧（ROS）产生增加以及小胶质细胞激活导致内皮/视网膜神经节细胞死亡。在这里，我们进行了体外和体内缺血/再灌注（I / R）功效研究的混合抗氧化剂-一氧化氮供体小分子，以评估其对眼部中风的治疗潜力。
为了诱导 I / R 损伤和炎症，我们将 R28 和原代小胶质细胞在体外进行氧葡萄糖剥夺（OGD）6 小时，或用 TNF-α、IL-1β和 IFN-γ混合物处理这些细胞 1 小时，然后加入 （10 μM）。测量小胶质细胞激活抑制、ROS 清除、细胞保护和抗炎活性。用 PBS 或 （2%）玻璃体腔内治疗体内 I / R 损伤的小鼠视网膜，并进行图形视网膜电图（ERG）、光谱域光学相干断层扫描、闪光 ERG 和视网膜免疫细胞化学。
显著抑制体外小胶质细胞激活和炎症。与对照组相比，该化合物显著减少了小胶质细胞（43%比 13%）和 R28 细胞（52%比 17%）中的细胞死亡，减少了视网膜小胶质细胞中 ROS（38%比 68%）的产生，保护了神经视网膜功能并增加了 SOD1 在小鼠眼中。
通过减少氧化应激和炎症细胞因子对视网膜神经元具有保护作用。
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