title: Short- and long-term corneal vascular effects of tafluprost eye drops.
abstract: BACKGROUND
  Prostaglandin analogs are first line therapy in the treatment of glaucoma, but also display side effects during ocular inflammation. In this context, the potential side effects of prostaglandin analogs on the normally avascular cornea, the main application route for eye drops, are so far not fully defined. Therefore, the aim of this study was to evaluate the vascular effects of the prostaglandin analog tafluprost on the healthy and inflamed cornea.
  
  
  METHODS
  For in vitro studies, blood and lymphatic endothelial cells were treated with tafluprost; cell proliferation was assessed after 48 h. For long-term in vivo studies under healthy conditions, naïve corneas of BALB/c mice were treated with tafluprost eye drops for 4 weeks. For short-term in vivo studies under inflammatory conditions, corneal inflammation was induced by suture placement; mice then received tafluprost eye drops for 1 week. Afterwards, corneas were stained with CD31 as panendothelial and LYVE-1 as lymphendothelial (and macrophage) marker.
  
  
  RESULTS
  In vitro, tafluprost did not alter blood or lymphatic endothelial cell proliferation. In vivo, there was no change in limbal blood or lymphatic vessel anatomy after long-term treatment with tafluprost. Short-term treatment with tafluprost under inflammatory conditions did not influence the recruitment of LYVE-1 positive macrophages into the cornea. Moreover, treatment of inflamed corneas with tafluprost did not significantly influence corneal hem- and lymphangiogenesis.
  
  
  CONCLUSIONS
  Tafluprost does not affect blood and lymphatic vessel growth, neither under resting nor under inflammatory conditions. These findings suggest a safe vascular profile of tafluprost eye drops at the inflammatory neovascularized cornea.
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany. deniz.hos@uk-koeln.de
authors.forename: Deniz
authors.initials: D
authors.lastname: Hos
authors.forename: Konrad R
authors.initials: KR
authors.lastname: Koch
authors.forename: Felix
authors.initials: F
authors.lastname: Bock
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Grajewski
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Dietlein
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
authors.forename: Ludwig M
authors.initials: LM
authors.lastname: Heindl
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply*; D016510:Corneal Neovascularization / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D007634:Keratitis / Q000378:metabolism / Q000503:physiopathology*; D042583:Lymphangiogenesis / Q000187:drug effects*; D042601:Lymphatic Vessels / Q000187:drug effects / Q000473:pathology; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009883:Ophthalmic Solutions; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011460:Prostaglandins F / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009883:Ophthalmic Solutions; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011460:Prostaglandins F; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C492273:LYVE1 protein, mouse; C467480:vascular endothelial growth factor A, mouse; C467483:vascular endothelial growth factor C, mouse; C485333:tafluprost