Steroid-Nitroxide Hybrid Compound Protects the Retina in a Model of CNV

Nitroxide-based drugs have proven effective in modulating radical-induced oxidative stress by modulating antioxidant enzymes and genes that control distinct immune and anti-inflammatory responses. Due to their reasonable chemical stability and ability to shuttle between oxidized and reduced forms at physiologically relevant redox potentials, nitroxide-based radicals have also proven effective as biological probes of redox status. Herein, we investigated the potential of a unique nitroxide-based antioxidant and anti-inflammatory agent to protect the retina from experimentally induced degeneration. An established rat model of retinal degeneration was used viz. laser-induced choroidal neovascularization (CNV) to study the effects of the hybrid steroidal anti-inflammatory-antioxidant prednisolone 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) nitroxide compound. Vascular endothelial cell distribution at the CNV lesion site was investigated using isolectin B4 fluorescence histology, and the inflammatory response of microglia was investigated using IBA-1 immunohistochemistry. The prednisolone-TEMPO (Pred-TEMPO) hybrid reduced the laser-induced CNV lesion area compared to untreated control rats. These findings demonstrate that nitroxide-based compounds are potential therapeutics for retinal degenerative diseases involving inflammatory and oxidative stress-mediated components, including age-related macular degeneration.