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

Abstract

BACKGROUND:

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.

• Authors: Melanie Lipp, Franziska Bucher, Anand Parthasarathy, Deniz Hos, Jasmine Onderka, Claus Cursiefen, Felix Bock
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 252 Issue 6 Pg. 943-9 (Jun 2014) ISSN: 1435-702X [Electronic] Germany
• PMID: 24728466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aptamers, Nucleotide
• Glycoproteins
• Membrane Transport Proteins
• Ophthalmic Solutions
• Platelet Endothelial Cell Adhesion Molecule-1
• Protein Isoforms
• Vascular Endothelial Growth Factor A
• Xlkd1 protein, mouse
• vascular endothelial growth factor A, mouse
• pegaptanib

Topics

• Administration, Topical
• Animals
• 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)
• Membrane Transport Proteins
• Mice
• Mice, Inbred BALB C
• Ophthalmic Solutions
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Protein Isoforms
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)