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Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis.

AbstractBACKGROUND:
The VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions.
METHODS:
The mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay.
RESULTS:
Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs.
CONCLUSIONS:
Targeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.
AuthorsMelanie Lipp, Franziska Bucher, Anand Parthasarathy, Deniz Hos, Jasmine Onderka, Claus Cursiefen, Felix Bock
JournalGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 252 Issue 6 Pg. 943-9 (Jun 2014) ISSN: 1435-702X [Electronic] Germany
PMID24728466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD31
  • Aptamers, Nucleotide
  • Glycoproteins
  • Ophthalmic Solutions
  • Protein Isoforms
  • Vascular Endothelial Growth Factor A
  • Xlkd1 protein, mouse
  • pegaptanib
  • vascular endothelial growth factor A, mouse
Topics
  • Administration, Topical
  • Animals
  • Antigens, CD31 (metabolism)
  • Aptamers, Nucleotide (pharmacology)
  • Cell Proliferation (drug effects)
  • Corneal Neovascularization (metabolism, pathology, prevention & control)
  • Disease Models, Animal
  • Endothelial Cells (metabolism, pathology)
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Glycoproteins (metabolism)
  • Lymphangiogenesis (physiology)
  • Mice
  • Mice, Inbred BALB C
  • Ophthalmic Solutions
  • Protein Isoforms
  • Vascular Endothelial Growth Factor A (antagonists & inhibitors)

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