{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:24:32Z","timestamp":1790202272099,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The normal cornea is transparent, which is essential for normal vision, and although the angiogenic factor vascular endothelial growth factor A (VEGF-A) is present in the cornea, its angiogenic activity is impeded by being bound to a soluble form of the VEGF receptor-1 (sVR-1). This report investigates the effect on the balance between VEGF-A and sVR-1 that occurs after ocular infection with HSV, which causes prominent neovascularization, an essential step in the pathogenesis of the vision-impairing lesion, stromal keratitis. We demonstrate that HSV-1 infection causes increased production of VEGF-A but reduces sVR-1 levels, resulting in an imbalance of VEGF-A and sVR-1 levels in ocular tissues. Moreover, the sVR-1 protein made was degraded by the metalloproteinase (MMP) enzymes MMP-2, -7, and -9 produced by infiltrating inflammatory cells that were principally neutrophils. Inhibition of neutrophils, inhibition of sVR-1 breakdown with the MMP inhibitor marimastat, and the provision of exogenous recombinant sVR-1 protein all resulted in reduced angiogenesis. Our results make the novel observation that ocular neovascularization resulting from HSV infection involves a change in the balance between VEGF-A and its soluble inhibitory receptor. Future therapies aimed to increase the production and activity of sVR-1 protein could benefit the management of stromal keratitis, an important cause of human blindness.<\/jats:p>","DOI":"10.4049\/jimmunol.1003239","type":"journal-article","created":{"date-parts":[[2011,2,17]],"date-time":"2011-02-17T03:58:08Z","timestamp":1297915088000},"page":"3653-3665","source":"Crossref","is-referenced-by-count":67,"title":["Ocular Neovascularization Caused by Herpes Simplex Virus Type 1 Infection Results from Breakdown of Binding between Vascular Endothelial Growth Factor A and Its Soluble Receptor"],"prefix":"10.1093","volume":"186","author":[{"given":"Amol","family":"Suryawanshi","sequence":"first","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Mulik","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep B J","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharvan","family":"Sehrawat","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry T","family":"Rouse","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Tennessee , Knoxville, TN 37996"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,3,15]]},"reference":[{"key":"2025032411134830000_r1","first-page":"264","article-title":"Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis)","volume":"104","author":"Azar","year":"2006","journal-title":"Trans. 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