Microglia activation and migration in retina during acute high-altitude exposure.

High-altitude retinopathy (HAR), caused by hypobaric hypoxia, leads to retinal dysfunction. However, its pathogenic mechanism remains elusive. Microglia, the resident immune cells of the retina, play crucial roles in various retinal disorders. Here, we investigated the functional alterations and underlying mechanisms of microglial activation in mouse models exposed to high-altitude (5000m HAE). Hematoxylin and eosin (H&E) staining showed edema in the entire, inner, and outer retinal layers after high-altitude exposure (HAE). Electroretinogram (ERG) testing revealed impaired retinal function under hypobaric hypoxia. Immunofluorescence staining confirmed a time-dependent increase in microglial numbers within the retina following HAE, with activated microglia migrating during persistent hypoxic injury. Furthermore, these activated microglia predominantly differentiated into pro-inflammatory subtypes under acute high-altitude conditions. Notably, Connexin43 (Cx43) immunoreactivity increased, while interleukin-1β (IL-1β) levels were markedly elevated at different time points after HAE. In this study, we confirmed that microglia activation and migration are involved in retinal edema and functional injury induced by hypobaric hypoxia. Additionally, the dynamic changes in Cx43 and up-regulation of IL-1β might be related to the inflammatory activation of microglia under acute HAE.