School of Biomedical Sciences
Permanent URI for this communityhttps://hdl.handle.net/20.500.12503/21585
Open Access scholarship from the School of Biomedical Sciences at the University of North Texas Health Science Center at Fort Worth.
Browse
Browsing School of Biomedical Sciences by Author "Acha, Lorea G."
Now showing 1 - 1 of 1
- Results Per Page
- Sort Options
Item Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models(MDPI, 2024-03-13) Amankwa, Charles E.; Acha, Lorea G.; Dibas, Adnan; Chavala, Sai H.; Roth, Steven; Mathew, Biji; Acharya, SuchismitaEmbolism, 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, SA-10, to assess its therapeutic potential for ocular stroke. METHODS: 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-alpha, IL-1beta and IFN-gamma for 1 h, followed by the addition of SA-10 (10 microM). 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 SA-10 (2%) intravitreally, and pattern electroretinogram (ERG), spectral-domain optical coherence tomography, flash ERG and retinal immunocytochemistry were performed. RESULTS: SA-10 significantly inhibited microglial activation and inflammation in vitro. Compared to the control, the compound SA-10 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. CONCLUSION: SA-10 is protective to retinal neurons by decreasing oxidative stress and inflammatory cytokines.