Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models

Date

2024-03-13

ORCID

0000-0001-5098-5555 (Acharya, Suchismita)

Journal Title

Journal ISSN

Volume Title

Publisher

MDPI

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-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.

Description

Citation

Amankwa, C. E., Acha, L. G., Dibas, A., Chavala, S. H., Roth, S., Mathew, B., & Acharya, S. (2024). Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models. Cells, 13(5), 396. https://doi.org/10.3390/cells13050396