Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis

Area of Science:

• Ophthalmology
• Vascular Biology
• Molecular Medicine

Background:

• Vascular Endothelial Growth Factor-A (VEGF-A) family is key in pathological corneal neovascularization.
• The specific roles of VEGF-A isoforms in lymphangiogenesis are not well understood.
• Current anti-angiogenic therapies non-selectively inhibit all VEGF-A isoforms, affecting both blood and lymphatic vessels.

Purpose of the Study:

• To investigate if selective targeting of the VEGF-A 165 isoform can inhibit corneal lymphangiogenesis during inflammation.
• To differentiate the roles of VEGF-A 165 in hemangiogenesis versus lymphangiogenesis.

Main Methods:

• Utilized a mouse model of suture-induced corneal neovascularization.
• Assessed the anti-hemangiogenic and anti-lymphangiogenic effects of topically applied pegaptanib.
• Analyzed corneal blood and lymph vascular areas morphometrically and performed in vitro cell-proliferation assays on endothelial cells with different VEGF-A isoforms.

Main Results:

• Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (blood vessel growth) both topically and systemically (p < 0.01).
• Pegaptanib did not significantly inhibit corneal lymphangiogenesis (lymphatic vessel growth) in vivo (p > 0.05).
• In vitro, blood endothelial cells (BECs) were more sensitive to pegaptanib than lymphatic endothelial cells (LECs).

Conclusions:

• Targeting VEGF-A 165 selectively inhibits hemangiogenesis but not lymphangiogenesis in the inflamed cornea.
• VEGF-A 165 appears critical for hemangiogenesis.
• VEGF-A 165 seems dispensable for lymphangiogenesis in the context of an inflamed cornea.