Microglia activation and migration in retina during acute high-altitude exposure
Yuting Li1, Cong Han2, Jianping Zhang2
1Department of Pathology, Basic Medical School, Ningxia Medical University, Yinchuan, 750004, PR China; Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, PR China.
Abstract:
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.
Insights
High-altitude exposure causes retinal dysfunction by activating microglia, leading to inflammation and edema. This study reveals microglial migration and pro-inflammatory changes are key mechanisms in high-altitude retinopathy.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- High-altitude retinopathy (HAR) is a retinal dysfunction caused by hypobaric hypoxia.
- The precise pathogenic mechanisms of HAR, particularly the role of microglia, remain unclear.
Purpose of the Study:
- To investigate microglial functional alterations and activation mechanisms in a mouse model of high-altitude exposure.
- To elucidate the role of microglia in retinal edema and functional impairment under hypobaric hypoxia.
Main Methods:
- Mouse models were exposed to high altitude (5000m HAE).
- Hematoxylin and eosin (H&E) staining, electroretinogram (ERG) testing, and immunofluorescence staining were performed.
- Changes in microglial numbers, activation status, Connexin43 (Cx43) immunoreactivity, and interleukin-1β (IL-1β) levels were assessed.
Main Results:
- High-altitude exposure induced retinal edema and impaired retinal function (ERG).
- Microglial numbers increased, and activated microglia migrated within the retina during hypoxic injury.
- Activated microglia showed a shift towards pro-inflammatory subtypes, with increased Cx43 and IL-1β levels.
Conclusions:
- Microglial activation and migration are integral to retinal edema and functional injury in hypobaric hypoxia.
- Dynamic changes in Cx43 and elevated IL-1β levels are associated with microglial inflammatory activation during acute high-altitude exposure.
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