NEUROPROTECTIVE EFFECTS OF DEXAMETHASONE IN ACUTE HIGH-ALTITUDE HYPOXIA-INDUCED NEURODEGENERATION OF RETINAL AND VISUAL CORTICAL NEURONS

Acute exposure to hypoxic environments is associated with several disorders, including high-altitude retinopathy (HAR), high-altitude cerebral edema, and retinal hemorrhages. HAR, in particular, reflects neurovascular dysfunction during systemic hypoxia, affecting retinal ganglion cells (RGCs) and the visual cortex, both highly susceptible to oxygen deprivation. We investigated whether pretreatment with dexamethasone could protect against hypobaric hypoxia–induced cellular damage in the retina and primary visual cortex using a rat model of HAR. Hypoxic injury was induced in a hypobaric chamber (FiO₂ = 16.6%) for 6 hours/day over 3 consecutive days. Animals in the treatment group received a single intraperitoneal dose of dexamethasone (1 mg/kg) prior to exposure. Histomorphological and ultrastructural analyses revealed that, following hypoxia, untreated rats exhibited significant thinning of the retinal layers, increased choroidal mast cell numbers, disruption of blood–brain barrier integrity, pronounced Müller cell swelling, and elevated apoptosis in the visual cortex. In contrast, dexamethasone-pretreated animals displayed preserved retinal layer architecture and barrier integrity, reduced mast cell activation, and decreased neuronal loss in the visual cortex. These findings indicate that dexamethasone pretreatment effectively mitigates hypoxia-induced neurovascular and neuronal damage, preserving the structural integrity of both retinal and cortical tissues under acute hypoxic conditions. The work was supported by the Higher Education and Science Committee of MESCS RA (Research project №. 25RG-1F181).