Ablation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model

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dc.creatorWilkerson, Joseph L.
dc.creatorBasu, Sandip K.
dc.creatorStiles, Megan A.
dc.creatorPrislovsky, Amanda
dc.creatorGrambergs, Richard C.
dc.creatorNicholas, Sarah E.
dc.creatorKaramichos, Dimitrios
dc.creatorAllegood, Jeremy C.
dc.creatorProia, Richard L.
dc.creatorMandal, Nawajes
dc.creator.orcid0000-0002-8761-3824 (Karamichos, Dimitrios)
dc.date.accessioned2023-02-07T21:55:46Z
dc.date.available2023-02-07T21:55:46Z
dc.date.issued2022-09-24
dc.description.abstractThe purpose of this study was to investigate the role of sphingosine kinase 1 (SphK1), which generates sphingosine-1-phosphate (S1P), in corneal neovascularization (NV). Wild-type (WT) and Sphk1 knockout (Sphk1(-/-)) mice received corneal alkali-burn treatment to induce corneal NV by placing a 2 mm round piece of Whatman No. 1 filter paper soaked in 1N NaOH on the center of the cornea for 20 s. Corneal sphingolipid species were extracted and identified using liquid chromatography/mass spectrometry (LC/MS). The total number of tip cells and those positive for ethynyl deoxy uridine (EdU) were quantified. Immunocytochemistry was done to examine whether pericytes were present on newly forming blood vessels. Cytokine signaling and angiogenic markers were compared between the two groups using multiplex assays. Data were analyzed using appropriate statistical tests. Here, we show that ablation of SphK1 can significantly reduce NV invasion in the cornea following injury. Corneal sphingolipid analysis showed that total levels of ceramides, monohexosyl ceramides (HexCer), and sphingomyelin were significantly elevated in Sphk(-/-) corneas compared to WT corneas, with a comparable level of sphingosine among the two genotypes. The numbers of total and proliferating endothelial tip cells were also lower in the Sphk1(-/-) corneas following injury. This study underscores the role of S1P in post-injury corneal NV and raises further questions about the roles played by ceramide, HexCer, and sphingomyelin in regulating corneal NV. Further studies are needed to unravel the role played by bioactive sphingolipids in maintenance of corneal transparency and clear vision.
dc.description.sponsorshipThis research was funded by the National Eye Institute, grants EY022071 (NM) and R01 EY031316 (NM and DK); the US Department of Defense Office of the Congressionally Directed Medical Research Programs (CDMRP), Vision Research Program (VRP) grant W81XWH-20-1-0900 (NM); Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory R&D (BLRD) grant I01 BX004893 (NM); and NIH grants P30 CA016059 and S10 RR031535 (VCU Lipidomics/Metabolomics Core).
dc.identifier.citationWilkerson, J. L., Basu, S. K., Stiles, M. A., Prislovsky, A., Grambergs, R. C., Nicholas, S. E., Karamichos, D., Allegood, J. C., Proia, R. L., & Mandal, N. (2022). Ablation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model. Cells, 11(18), 2914. https://doi.org/10.3390/cells11182914
dc.identifier.issn2073-4409
dc.identifier.issue18
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32010
dc.identifier.volume11
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cells11182914
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.sourceCells
dc.subjectneovascularization
dc.subjectsphingolipid
dc.subjectsphingosine kinase 1
dc.subjectsphingosine-1-phosphate
dc.subject.meshAnimals
dc.subject.meshCeramides
dc.subject.meshCornea
dc.subject.meshCorneal Injuries
dc.subject.meshCytokines
dc.subject.meshDisease Models, Animal
dc.subject.meshLysophospholipids
dc.subject.meshMice
dc.subject.meshNeovascularization, Pathologic
dc.subject.meshPhosphotransferases (Alcohol Group Acceptor)
dc.subject.meshSodium Hydroxide
dc.subject.meshSphingolipids
dc.subject.meshSphingomyelins
dc.subject.meshSphingosine / analogs & derivatives
dc.subject.meshSphingosine / pharmacology
dc.subject.meshUridine
dc.titleAblation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model
dc.typeArticle
dc.type.materialtext

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