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

Mesentier-Louro, Louise A.; Rangel, Barbara; Stell, Laurel; Shariati, M. Ali; Dalal, Roopa; Nathan, Abinaya; Yuan, Ke; Perez, Vinicio de Jesus; Liao, Yaping Joyce

doi:10.1371/journal.pone.0246681

Cited by 10 publications

(6 citation statements)

References 100 publications

(138 reference statements)

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“…The emergence of NAION in response to hypobaric hypoxia can be attributed to failure of retinal circulatory autoregulation in the face of decreased SaO 2 and perfusion pressure, with the concomitant increase in venous pressure. Hypoxia-induced oxidative stress, glial cell dysfunction, and up-regulation of inflammatory pathways [ 148 , 149 ] have also been suggested to play a role.…”

Section: Discussionmentioning

confidence: 99%

Impact of flight and equivalent short-term high-altitude exposure on ocular structures and function

Totou,

Karmiris,

Kanakis

et al. 2023

Med Hypothesis Discov Innov Ophthalmol

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Background: Exposure to high-altitude conditions during flight or similar activities affects many aspects of visual function, which is critical not only for flight safety but for any altitude-related activity. We aimed to summarize the available literature pertaining to ocular changes during flight or equivalent short-term high-altitude exposure (e.g., hypobaric chamber, effortless ascent lasting less than or equal to 24 h) and to highlight future research priorities. Methods: Using the PubMed/MEDLINE and Web of Science/ISI Web of Knowledge databases with structured search syntax, we conducted a systematic review of the literature spanning a 40-year period (January 1, 1983, to October 10, 2023). Articles pertaining to ocular changes during flight or flight-equivalent exposure to altitude were retrieved. The reference lists of retrieved studies were also searched, and citations of these references were included in the results. Results: Of 875 relevant PubMed and ISI publications, 122 qualified for inclusion and 20 more were retrieved from the reference lists of initially selected records, for a total of 142 articles. Reported anterior segment changes included deterioration in tear film stability and increased dry eye incidence, increased corneal thickness, discomfort and bubble formation in contact lens users, refraction changes in individuals with prior refractive surgery, decreased intraocular pressure, and alterations in pupillary reaction, contrast sensitivity, and visual fields. Photoreceptor–visual pathway changes included alterations in both photoreceptors and neuro-transduction, as evidenced in dark adaptation, macular recovery time, reduction in visual field sensitivity, and optic neuritis (likely an element of decompression sickness). Retinochoroidal changes included increases in retinal vessel caliber, retinal blood flow, and choroidal thickness; central serous chorioretinopathy; and retinal vascular events (non-arteritic ischemic optic neuropathy, high-altitude retinopathy, and retinal vein occlusion). Conclusions: The effect of short-term high-altitude exposure on the eye is, in itself, a difficult area to study. Although serious impairment of visual acuity appears to be rare, ocular changes, including tear film stability, contact lens wear, central corneal thickness, intraocular pressure, contrast sensitivity, stability of refractive surgeries, retinal vessels, visual fields, and macula recovery time, should be considered in civilian aviators. Our report provides guidance to climbers and lowlanders traveling to altitude if they have pre-existing ocular conditions or if they experience visual symptoms while at altitude. However, key outcomes have been contradictory and comprehensive studies are scarce, especially those pertaining to the choroid and retina. Such studies could not only deepen our understanding of high-altitude ocular pathophysiology, but could also offer valuable information and treatment possibilities for a constellation of other vision-threatening diseases.

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Section: Discussionmentioning

confidence: 99%

Impact of flight and equivalent short-term high-altitude exposure on ocular structures and function

Totou,

Karmiris,

Kanakis

et al. 2023

Med Hypothesis Discov Innov Ophthalmol

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“…A regionally restricted oxygen perfusion is a cyclic/chronic hypoxic environment that can lead to degenerative pathologies such as hypertrophy, atrophy, fibrosis, and neoplasm due to developing localized hypoxia ( Figure 1 ). Examples of such a range of hypoxic degenerative pathologies can be seen in acute high-altitude hypoxia (hypobaric hypoxia) organ hypertrophy ( Pena et al, 2022 ) and tissue edema ( Mesentier-Louro et al, 2021 ). Others include androgen deprivation therapy promoting epithelial–mesenchymal transition ( Byrne et al, 2016 ), cancer-associated fibroblasts ( Kim I. et al, 2022 ), and prostate cancer progression metastasis ( Mohamed et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

“…Both oxidative stress and inflammation are driven by hypoxia ( Biddlestone et al, 2015 ; McGarry et al, 2018 ; Korbecki et al, 2021 ; Mesentier-Louro et al, 2021 ), which could explain why anti-oxidative therapies alone cannot restore cellular redox homeostasis ( Tretter et al, 2021 ). Endothelial cell biology of functions and dysfunctions ( Charreau, 2022 ) is an emerging approach to understanding microvascular endothelial heterogeneity and inflammation ( Yang et al, 2021c ; Rossi et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Understanding human aging and the fundamental cell signaling link in age-related diseases: the middle-aging hypovascularity hypoxia hypothesis

Phua

2023

Front. Aging

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Aging-related hypoxia, oxidative stress, and inflammation pathophysiology are closely associated with human age-related carcinogenesis and chronic diseases. However, the connection between hypoxia and hormonal cell signaling pathways is unclear, but such human age-related comorbid diseases do coincide with the middle-aging period of declining sex hormonal signaling. This scoping review evaluates the relevant interdisciplinary evidence to assess the systems biology of function, regulation, and homeostasis in order to discern and decipher the etiology of the connection between hypoxia and hormonal signaling in human age-related comorbid diseases. The hypothesis charts the accumulating evidence to support the development of a hypoxic milieu and oxidative stress-inflammation pathophysiology in middle-aged individuals, as well as the induction of amyloidosis, autophagy, and epithelial-to-mesenchymal transition in aging-related degeneration. Taken together, this new approach and strategy can provide the clarity of concepts and patterns to determine the causes of declining vascularity hemodynamics (blood flow) and physiological oxygenation perfusion (oxygen bioavailability) in relation to oxygen homeostasis and vascularity that cause hypoxia (hypovascularity hypoxia). The middle-aging hypovascularity hypoxia hypothesis could provide the mechanistic interface connecting the endocrine, nitric oxide, and oxygen homeostasis signaling that is closely linked to the progressive conditions of degenerative hypertrophy, atrophy, fibrosis, and neoplasm. An in-depth understanding of these intrinsic biological processes of the developing middle-aged hypoxia could provide potential new strategies for time-dependent therapies in maintaining healthspan for healthy lifestyle aging, medical cost savings, and health system sustainability.

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“…HA-NAION is rare and may be related to adaptive changes in retinal autoregulation in response to hypobaric hypoxia (13). In preclinical studies, exposure to systemic hypoxia leads to endoplasmic reticulum stress, glial cell reactivity and loss, retinal thickness changes, and upregulation of inflammatory pathways (14,15). This is consistent with increased inflammatory biomarkers in the blood of patients with NAION (16).…”

Section: Discussionmentioning

confidence: 99%

High Altitude as a Risk Factor for the Development of Nonarteritic Anterior Ischemic Optic Neuropathy

Liu¹,

Mesentier-Louro²,

Shariati³

et al. 2022

Journal of Neuro-Ophthalmology

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Background:Episodic high-altitude exposure leads to optic disc edema and retinopathy. It is uncertain whether high-altitude exposure is a risk factor for nonarteritic anterior ischemic optic neuropathy (NAION).Methods:We performed a single-center, retrospective, cross-sectional case study of 5 patients with high-altitude–associated NAION (HA-NAION) from April 2014 to April 2019. Main study parameters included known vascular risk factors for NAION, evolution of visual acuity, visual field, optic disc, and macula measurements.Results:We studied 5 eyes of 5 patients with HA-NAION that occurred at 7,000–9,000 ft above sea level, 28 patients with classic NAION that developed at sea level (normal altitude NAION or NA-NAION), and 40 controls. All 5 patients with HA-NAION had clinically confirmed NAION by a neuro-ophthalmologist within 3–21 days of onset and comprehensive follow-up evaluations (average follow-up of 23 months). Other than high-altitude exposure, 4 of 5 patients had undiagnosed obstructive sleep apnea (OSA, apnea–hypopnea index 5.4–22.2) and 1 had systemic vascular risk factors. All patients had disc-at-risk in the contralateral eye. The best-corrected distance visual acuity was 20/20 to 20/70 (median logMAR 0) at presentation and 20/70 to counting finger (median logMAR 0) at ≥6 months. Automated static perimetry revealed average mean deviation of −18.6 dB at presentation and −22.1 dB at ≥6 months. The average retinal nerve fiber layer was 244 µm (80–348 µm) at onset and 59 µm (55–80 µm) at ≥6 months. The average ganglion cell complex thickness was 50 µm (43–54 µm) at onset and 52 µm (50–55 µm) at ≥6 months. The patients with OSA were started on home continuous positive airway pressure treatment. Visual outcomes were similar in patients with HA-NAION and NA-NAION. - After addressing all NAION risk factors, no new events occurred in the HA-NAION group within 2-8 years with or without repeat high-altitude exposure.Conclusions:NAION can occur under high-altitude conditions. HA-NAION is associated with relatively younger age at onset, disc-at-risk, and OSA. These patients exhibit a relatively progressive course of vision loss after initial onset and severe thinning of optic nerves on optical coherence tomography. Treatment for OSA is recommended, especially with repeated high-altitude exposure.

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

Cited by 10 publications

References 100 publications

Impact of flight and equivalent short-term high-altitude exposure on ocular structures and function

Impact of flight and equivalent short-term high-altitude exposure on ocular structures and function

Understanding human aging and the fundamental cell signaling link in age-related diseases: the middle-aging hypovascularity hypoxia hypothesis

High Altitude as a Risk Factor for the Development of Nonarteritic Anterior Ischemic Optic Neuropathy

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