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Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes
Louise A Mesentier-Louro1, Barbara Rangel1, Laurel Stell2
1Department of Ophthalmology, Stanford University, School of Medicine, Stanford, California, United States of America.
Plos One
|March 4, 2021
Summary
Systemic hypoxia rapidly causes retinal inflammation and edema by altering immune molecules and glial function. These changes resolve within 24 hours, suggesting potential biomarkers for hypoxia-induced vision loss.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Systemic hypoxia, often seen in cardiopulmonary diseases like SARS-CoV-2 infection or high-altitude exposure, can lead to central nervous system and visual dysfunction.
- Hypoxia-induced inflammatory signaling is implicated in retinal inflammation, gliosis, and visual disturbances.
Purpose of the Study:
- To investigate the immediate consequences of systemic hypoxia on the retina.
- To identify early molecular and histological changes within 24 hours post-hypoxia.
Main Methods:
- Induction of severe systemic hypoxia (10% O2) in adult C57BL/6 mice for one week.
- Serial retinal optical coherence tomography (OCT) and retinal histology.
- Proteomics analysis of 39 cytokines, chemokines, and growth factors in plasma and retina at 1h and 18h post-hypoxia.
Main Results:
- Retinal tissue edema was observed via OCT at 18 hours post-hypoxia.
- Proteomics revealed significant changes in immune molecules, with increased Interleukin-1β and vascular endothelial growth factor in both plasma and retina at 1h.
- Histology showed increased aquaporin-4, decreased Kir4.1, and gliosis in retinal tissue.
Conclusions:
- The immediate post-hypoxic period is marked by systemic and retinal inflammation and glial changes affecting water transport, leading to edema.
- These inflammatory changes resolve within 24 hours, aligning with transient visual disturbances in conditions like high-altitude retinopathy.
- Further research involving plasma immune profiling and in vivo retinal imaging in at-risk patients is crucial for identifying biomarkers of visual impairment in systemic hypoxia.

