Dexamethasone pretreatment attenuates hypobaric hypoxia-induced histomorphological alterations in the rat retina and primary visual cortex.

Exposure to acute hypoxic environments is associated with several ocular disorders, including high-altitude retinopathy (HAR), optic disc edema, retinal hemorrhage, and temporary vision loss. These alterations arise primarily from hypobaric hypoxia and impaired vascular autoregulation. HAR, in particular, is a key indicator of neurovascular dysfunction during systemic hypoxia, affecting retinal ganglion cells-the main output neurons of the retina-as well as the visual cortex, both of which are highly vulnerable to oxygen deprivation. In this study, we investigated the potential protective role of dexamethasone pretreatment against acute intermittent hypobaric hypoxia-induced cellular damage in the retina and primary visual cortex using a rat model of simulated high-altitude exposure. Hypoxic injury was induced in a hypobaric chamber (FiO2=16.6%, pO2=61 mmHg) for 6 hours during 3 consecutive days. Animals in the pretreated group received intraperitoneal injections of dexamethasone (1 mg/kg) once daily for three consecutive days before each hypoxic exposure session. Following hypoxia, untreated rats exhibited significant elevation in retinal layer thickness, increased numbers of choroidal mast cells along with degranulation in the connective tissue around the eyeball, pronounced Müller cell swelling, and neurodegenerative changes in the visual cortex. In contrast, dexamethasone-pretreated animals showed preserved retinal layer cytoarchitecture, reduced choroidal mast cell number, and decreased neuronal loss in the visual cortex. Overall, these findings demonstrate that dexamethasone pretreatment effectively preserves the structural integrity of both the retina and the visual cortex under acute hypoxic conditions.