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Wild-type (WT) and Sphk1 knockout (Sphk1\u2212\/\u2212) 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\u2212\/\u2212 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/cells11182914","type":"journal-article","created":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T22:12:43Z","timestamp":1663539163000},"page":"2914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ablation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-7589","authenticated-orcid":false,"given":"Joseph L.","family":"Wilkerson","sequence":"first","affiliation":[{"name":"Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip K.","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Stiles","sequence":"additional","affiliation":[{"name":"Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Prislovsky","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Grambergs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Nicholas","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Karamichos","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy C.","family":"Allegood","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-1270","authenticated-orcid":false,"given":"Richard L.","family":"Proia","sequence":"additional","affiliation":[{"name":"Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-7748","authenticated-orcid":false,"given":"Nawajes","family":"Mandal","sequence":"additional","affiliation":[{"name":"Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA"},{"name":"Departments of Anatomy and Neurobiology, and Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA"},{"name":"Memphis VA Medical Center, Memphis, TN 38104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1097\/00003226-200111000-00015","article-title":"Enigma of the abundant water-soluble cytoplasmic proteins of the cornea: The \u201crefracton\u201d hypothesis","volume":"20","author":"Piatigorsky","year":"2001","journal-title":"Cornea"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"061006","DOI":"10.1115\/1.2982251","article-title":"Three-dimensional modeling and computational analysis of the human cornea considering distributed collagen fibril orientations","volume":"130","author":"Pandolfi","year":"2008","journal-title":"J. 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