Ocular Hypertension Results in Hypoxia within Glia and Neurons throughout the Visual Projection

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dc.creatorJassim, Assraa Hassan
dc.creatorNsiah, Nana Yaa
dc.creatorInman, Denise M.
dc.creator.orcid0000-0002-8522-4112 (Inman, Denise M.)
dc.date.accessioned2022-09-20T15:20:18Z
dc.date.available2022-09-20T15:20:18Z
dc.date.issued2022-04-29
dc.description.abstractThe magnitude and duration of hypoxia after ocular hypertension (OHT) has been a matter of debate due to the lack of tools to accurately report hypoxia. In this study, we established a topography of hypoxia in the visual pathway by inducing OHT in mice that express a fusion protein comprised of the oxygen-dependent degradation (ODD) domain of HIF-1alpha and a tamoxifen-inducible Cre recombinase (CreERT2) driven by a ubiquitous CAG promoter. After tamoxifen administration, tdTomato expression would be driven in cells that contain stabilized HIF-1alpha. Intraocular pressure (IOP) and visual evoked potential (VEP) were measured after OHT at 3, 14, and 28 days (d) to evaluate hypoxia induction. Immunolabeling of hypoxic cell types in the retina and optic nerve (ON) was performed, as well as retinal ganglion cell (RGC) and axon number quantification at each time point (6 h, 3 d, 14 d, 28 d). IOP elevation and VEP decrease were detected 3 d after OHT, which preceded RGC soma and axon loss at 14 and 28 d after OHT. Hypoxia was detected primarily in Muller glia in the retina, and microglia and astrocytes in the ON and optic nerve head (ONH). Hypoxia-induced factor (HIF-alpha) regulates the expression of glucose transporters 1 and 3 (GLUT1, 3) to support neuronal metabolic demand. Significant increases in GLUT1 and 3 proteins were observed in the retina and ON after OHT. Interestingly, neurons and endothelial cells within the superior colliculus in the brain also experienced hypoxia after OHT as determined by tdTomato expression. The highest intensity labeling for hypoxia was detected in the ONH. Initiation of OHT resulted in significant hypoxia that did not immediately resolve, with low-level hypoxia apparent out to 14 and 28 d, suggesting that continued hypoxia contributes to glaucoma progression. Restricted hypoxia in retinal neurons after OHT suggests a hypoxia management role for glia.
dc.description.sponsorshipThis research was funded by the National Institutes of Health, National Eye Institute, NIH EY026662 (to DMI).
dc.identifier.citationJassim, A. H., Nsiah, N. Y., & Inman, D. M. (2022). Ocular Hypertension Results in Hypoxia within Glia and Neurons throughout the Visual Projection. Antioxidants (Basel, Switzerland), 11(5), 888. https://doi.org/10.3390/antiox11050888
dc.identifier.issn2076-3921
dc.identifier.issue5
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31778
dc.identifier.volume11
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/antiox11050888
dc.rights.holder© 2022 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceAntioxidants (Basel)
dc.subjectMuller glia
dc.subjectastrocytes
dc.subjectglaucoma
dc.subjecthypoxia
dc.subjectmicroglia
dc.subjectretinal ganglion cells
dc.titleOcular Hypertension Results in Hypoxia within Glia and Neurons throughout the Visual Projection
dc.typeArticle
dc.type.materialtext

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