Systemic hypoxia led to little retinal neuronal loss and dramatic optic nerve glial response

Mesentier-Louro, Louise A.; Shariati, M. Ali; Dalal, Roopa; Camargo, Alexandra; Kumar, Varun; Shamskhou, Elya; Perez, Vinicio de Jesus; Liao, Yaping Joyce

doi:10.1016/j.exer.2020.107957

Cited by 21 publications

(32 citation statements)

References 84 publications

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“…However, murine models with 48 hours of systemic hypoxia (10% O 2 ) have shown glial dysfunction, but no neural changes. 7 Interestingly, it has been T A B L E 1 Clinical characteristics and peripapillary optical coherence tomography findings suggested that the asymptomatic hypoxemia presented by some COVID-19 patients with severe pneumonia is related to a dysfunction of cortical, and is associated with neuroinvasion of the virus.…”

Section: Optical Coherence Tomography (Oct) Is a Noninvasive Imagingmentioning

confidence: 99%

Optic nerve analysis in COVID‐19 patients

Burgos-Blasco

Güemes-Villahoz

Donate-López

et al. 2020

Journal of Medical Virology

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Section: Optical Coherence Tomography (Oct) Is a Noninvasive Imagingmentioning

confidence: 99%

Optic nerve analysis in COVID‐19 patients

Burgos-Blasco

Güemes-Villahoz

Donate-López

et al. 2020

Journal of Medical Virology

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“…Previous studies in systemic hypoxia in humans and animals, including from our laboratory, have shown that hypoxia is associated with retinal and optic nerve structural changes consistent with edema and inflammation and that retinal and optic nerve glial changes predominate after 48h hypoxia [ 30 ], while retinal vascular changes are common after 3-week hypoxia [ 36 ]. In this study, we examined the retinal, optic nerve, and plasma changes after 1-week hypoxia–a clinically relevant time point–and found that by 18h of posthypoxic recovery, serial OCT revealed significant new thickening of the peripapillary retina consistent with posthypoxic retinal edema.…”

Section: Discussionmentioning

confidence: 99%

“…Human OCT studies showed increased thickness of the retinal nerve fiber layer and ganglion cell layer after ascent to high altitude [ 21 , 29 ]. OCT is fast, non-invasive and easy to perform in humans and animals, making it extremely useful to monitor changes in the retina, including at shorter exposures to hypoxia [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…In animal models, we have previously described that 48h systemic hypoxia caused limited cell loss in the outer retina and no neuronal loss in the inner retina, but induced prominent optic nerve glia response, endoplasmic reticulum stress and loss of oligodendrocytes [ 30 ], which can lead to axonal dysfunction and visual disturbance due to impaired saltatory signal transmission. In the cerebral cortex, hypobaric hypoxia leads to a progressive increase in the levels of hypoxia-inducible factor 1- a , vascular endothelial growth factor (VEGF) and Angiopoietin-2, all of which plateau or decrease after the first week in hypoxia [ 31 ], suggesting that important molecular signaling occur in the CNS within one week of hypoxia.…”

Section: Introductionmentioning

confidence: 99%

“…To assess posthypoxic inflammation, we profiled retinal and plasma inflammatory and other molecular changes using a Luminex 39-immune molecule assay. Finally, we analyzed retinal and optic nerve histologic changes and compared them with that of OCT and immune profiling, with focus on glial cells in the retina and optic nerve, since we found that glial cells were most impacted after 48h hypoxia [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes

et al. 2021

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Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology. We induced severe systemic hypoxia in adult C57BL/6 mice using a hypoxia chamber (10% O2) for 1 week and rapidly assessed measurements within 1h compared with 18h after hypoxia. Optical coherence tomography revealed retinal tissue edema at 18h after hypoxia. Hierarchical clustering of plasma and retinal immune molecules revealed obvious segregation of the 1h posthypoxia group away from that of controls. One hour after hypoxia, there were 10 significantly increased molecules in plasma and 4 in retina. Interleukin-1β and vascular endothelial growth factor were increased in both tissues. Concomitantly, there was significantly increased aquaporin-4, decreased Kir4.1, and increased gliosis in retinal histology. In summary, the immediate posthypoxic period is characterized by molecular changes consistent with systemic and retinal inflammation and retinal glial changes important in water transport, leading to tissue edema. This posthypoxic inflammation rapidly improves within 24h, consistent with the typically mild and transient visual disturbance in hypoxia, such as in high-altitude retinopathy. Given hypoxia increases risk of vision loss, more studies in at-risk patients, such as plasma immune profiling and in vivo retinal imaging, are needed in order to identify novel diagnostic or prognostic biomarkers of visual impairment in systemic hypoxia.

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Compartmentalized ciliation changes of oligodendrocytes in aged mouse optic nerve

Ning,

Tran,

Kowal

et al. 2023

J of Neuroscience Research

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Primary cilia are microtubule‐based sensory organelles that project from the apical surface of most mammalian cells, including oligodendrocytes, which are myelinating cells of the central nervous system (CNS) that support critical axonal function. Dysfunction of CNS glia is associated with aging‐related white matter diseases and neurodegeneration, and ciliopathies are known to affect CNS white matter. To investigate age‐related changes in ciliary profile, we examined ciliary length and frequency in the retinogeniculate pathway, a white matter tract commonly affected by diseases of aging but in which expression of cilia has not been characterized. We found expression of Arl13b, a marker of primary cilia, in a small group of Olig2‐positive oligodendrocytes in the optic nerve, optic chiasm, and optic tract in young and aged C57BL/6 wild‐type mice. While the ciliary length and ciliated oligodendrocyte cells were constant in young mice in the retinogeniculate pathway, there was a significant increase in ciliary length in the anterior optic nerve as compared to the aged animals. Morphometric analysis confirmed a specific increase in the ciliation rate of CC1+/Olig2+ oligodendrocytes in aged mice compared with young mice. Thus, the prevalence of primary cilia in oligodendrocytes in the visual pathway and the age‐related changes in ciliation suggest that they may play important roles in white matter and age‐associated optic neuropathies.

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Systemic hypoxia led to little retinal neuronal loss and dramatic optic nerve glial response

Cited by 21 publications

References 84 publications

Optic nerve analysis in COVID‐19 patients

Optic nerve analysis in COVID‐19 patients

Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes

Compartmentalized ciliation changes of oligodendrocytes in aged mouse optic nerve

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