title: Robo 4 Counteracts Angiogenesis in Herpetic Stromal Keratitis.
abstract: The cornea is a complex tissue that must preserve its transparency to maintain optimal vision. However, in some circumstances, damage to the eye can result in neovascularization that impairs vision. This outcome can occur when herpes simplex virus type 1 (HSV-1) causes the immunoinflammatory lesion stromal keratitis (SK). Potentially useful measures to control the severity of SK are to target angiogenesis which with herpetic SK invariably involves VEGF. One such way to control angiogenesis involves the endothelial receptor Robo4 (R4), which upon interaction with another protein activates an antiangiogenic pathway that counteracts VEGF downstream signaling. In this study we show that mice unable to produce R4 because of gene knockout developed significantly higher angiogenesis after HSV-1 ocular infection than did infected wild type (WT) controls. Moreover, providing additional soluble R4 (sR4) protein by subconjunctival administration to R4 KO HSV-1 infected mice substantially rescued the WT phenotype. Finally, administration of sR4 to WT HSV-1 infected mice diminished the extent of corneal angiogenesis compared to WT control animals. Our results indicate that sR4 could represent a useful therapeutic tool to counteract corneal angiogenesis and help control the severity of SK.
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN, 37996, United States of America.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Gimenez
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN, 37996, United States of America.|Immune Disease Institute and Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Sachin
authors.initials: S
authors.lastname: Mulik
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN, 37996, United States of America.
authors.forename: Tamara
authors.initials: T
authors.lastname: Veiga-Parga
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN, 37996, United States of America.
authors.forename: Siddheshvar
authors.initials: S
authors.lastname: Bhela
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 1414 Cumberland Avenue, Knoxville, TN, 37996, United States of America.
authors.forename: Barry T
authors.initials: BT
authors.lastname: Rouse
mesh_terms: D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D018259:Herpesvirus 1, Human; D016849:Keratitis, Herpetic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000494:pharmacology; D010641:Phenotype; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C540792:Robo4 protein, mouse; D042461:Vascular Endothelial Growth Factor A