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- Title
Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models.
- Authors
Amankwa, Charles E.; Acha, Lorea Gamboa; Dibas, Adnan; Chavala, Sai H.; Roth, Steven; Mathew, Biji; Acharya, Suchismita
- Abstract
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, 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-α, IL-1β and IFN-γ for 1 h, followed by the addition of SA-10 (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 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.
- Subjects
RETINAL injuries; ANTI-inflammatory agents; RETINAL ganglion cells; CELL death; OPTICAL coherence tomography; REACTIVE oxygen species
- Publication
Cells (2073-4409), 2024, Vol 13, Issue 5, p396
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells13050396