Distinct Metabolic Profiles of Ocular Hypertensives in Response to Hypoxia
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Distinct Metabolic Profiles of Ocular Hypertensives in Response to Hypoxia. / Langbøl, Mia; Rovelt, Jens; Saruhanian, Arevak; Saruhanian, Sarkis; Tiedemann, Daniel; Baskaran, Thisayini; Bocca, Cinzia; Vohra, Rupali; Cvenkel, Barbara; Lenaers, Guy; Kolko, Miriam.
In: International Journal of Molecular Sciences, Vol. 25, No. 1, 195, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Distinct Metabolic Profiles of Ocular Hypertensives in Response to Hypoxia
AU - Langbøl, Mia
AU - Rovelt, Jens
AU - Saruhanian, Arevak
AU - Saruhanian, Sarkis
AU - Tiedemann, Daniel
AU - Baskaran, Thisayini
AU - Bocca, Cinzia
AU - Vohra, Rupali
AU - Cvenkel, Barbara
AU - Lenaers, Guy
AU - Kolko, Miriam
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2024
Y1 - 2024
N2 - Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs). The main risk factor is elevated intraocular pressure (IOP), but the actual cause of the disease remains unknown. Emerging evidence indicates that metabolic dysfunction plays a central role. The aim of the current study was to determine and compare the effect of universal hypoxia on the metabolomic signature in plasma samples from healthy controls (n = 10), patients with normal-tension glaucoma (NTG, n = 10), and ocular hypertension (OHT, n = 10). By subjecting humans to universal hypoxia, we aim to mimic a state in which the mitochondria in the body are universally stressed. Participants were exposed to normobaric hypoxia for two hours, followed by a 30 min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and in recovery. Plasma samples were analyzed using a non-targeted metabolomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and univariate analysis using the Wilcoxon signed-rank test and false discovery rate (FDR) correction. Unique metabolites involved in fatty acid biosynthesis and ketone body metabolism were upregulated, while metabolites of the kynurenine pathway were downregulated in OHT patients exposed to universal hypoxia. Differential affection of metabolic pathways may explain why patients with OHT initially do not suffer or are more resilient from optic nerve degeneration. The metabolomes of NTG and OHT patients are regulated differently from control subjects and show dysregulation of metabolites important for energy production. These dysregulated processes may potentially contribute to the elevation of IOP and, ultimately, cell death of the RGCs.
AB - Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs). The main risk factor is elevated intraocular pressure (IOP), but the actual cause of the disease remains unknown. Emerging evidence indicates that metabolic dysfunction plays a central role. The aim of the current study was to determine and compare the effect of universal hypoxia on the metabolomic signature in plasma samples from healthy controls (n = 10), patients with normal-tension glaucoma (NTG, n = 10), and ocular hypertension (OHT, n = 10). By subjecting humans to universal hypoxia, we aim to mimic a state in which the mitochondria in the body are universally stressed. Participants were exposed to normobaric hypoxia for two hours, followed by a 30 min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and in recovery. Plasma samples were analyzed using a non-targeted metabolomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and univariate analysis using the Wilcoxon signed-rank test and false discovery rate (FDR) correction. Unique metabolites involved in fatty acid biosynthesis and ketone body metabolism were upregulated, while metabolites of the kynurenine pathway were downregulated in OHT patients exposed to universal hypoxia. Differential affection of metabolic pathways may explain why patients with OHT initially do not suffer or are more resilient from optic nerve degeneration. The metabolomes of NTG and OHT patients are regulated differently from control subjects and show dysregulation of metabolites important for energy production. These dysregulated processes may potentially contribute to the elevation of IOP and, ultimately, cell death of the RGCs.
KW - energy metabolism
KW - glaucoma
KW - hypoxia
KW - metabolomics
KW - normal-tension glaucoma
KW - ocular hypertension
KW - oxygen stress
U2 - 10.3390/ijms25010195
DO - 10.3390/ijms25010195
M3 - Journal article
C2 - 38203366
VL - 25
JO - International Journal of Molecular Sciences (CD-ROM)
JF - International Journal of Molecular Sciences (CD-ROM)
SN - 1424-6783
IS - 1
M1 - 195
ER -
ID: 379199209