Reactive oxygen species play a significant role in the pathogenesis of various ocular neurodegenerative diseases especially glaucoma, age-related macular degeneration (AMD), and ocular ischemic stroke. Increased oxidative stress and the accumulation of ROS have been implicated in the progression of these diseases. As a result, there has been growing interest in exploring potential therapeutic and prophylactic strategies involving exogenous antioxidants. In recent years, there have been significant advancements in the development of synthetic therapeutic antioxidants for targeting reactive oxygen species (ROS) in neurodegenerative diseases. One area of focus has been the development of hybrid TEMPOL derivatives. In the context of ocular diseases, the application of next-generation hybrid TEMPOL antioxidants may offer new avenues for neuroprotection. By targeting ROS and reducing oxidative stress in the retina and optic nerve, these compounds have the potential to preserve retinal ganglion cells and trabecular meshwork and protect against optic nerve damage, mitigating irreversible blindness associated with these diseases. This review seeks to highlight the potential impact of hybrid TEMPOL antioxidants and their derivatives on ocular neurodegenerative disorders.

Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent complete or partial occlusion of the airway. Despite a recognized association between OSA and glaucoma, the nature of the underlying link remains unclear. In this study, we investigated whether mild OSA induces morphological, inflammatory, and metabolic changes in the retina resembling those seen in glaucoma using a rat model of OSA known as chronic intermittent hypoxia (CIH). Rats were randomly assigned to either normoxic or CIH groups. The CIH group was exposed to periodic hypoxia during its sleep phase with oxygen reduction from 21% to 10% and reoxygenation in 6 min cycles over 8 h/day. The eyes were subsequently enucleated, and then the retinas were evaluated for retinal ganglion cell number, oxidative stress, inflammatory markers, metabolic changes, and hypoxic response modulation using immunohistochemistry, multiplex assays, and capillary electrophoresis. Statistically significant differences were observed between normoxic and CIH groups for oxidative stress and inflammation, with CIH resulting in increased HIF-1α protein levels, higher oxidative stress marker 8-OHdG, and increased TNF-α. Pyruvate dehydrogenase kinase-1 protein was significantly reduced with CIH. No significant differences were found in retinal ganglion cell number. Our findings suggest that CIH induces oxidative stress, inflammation, and upregulation of HIF-1α in the retina, akin to early-stage glaucoma.