Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility.

Area of Science:

• Ophthalmology
• Cell Biology
• Physiology

Background:

• Anti-vascular endothelial growth factor (VEGF) antibody therapy is a key treatment for ocular angiogenesis.
• Elevated intraocular pressure is a known side effect in some patients undergoing anti-VEGF therapy.
• The specific impact of VEGF-A on the aqueous humor outflow pathway remains largely uncharacterized.

Purpose of the Study:

• To investigate the effects of VEGF-A on the aqueous humor outflow pathway.
• To determine if VEGF-A influences the permeability of trabecular meshwork (TM) and Schlemm's canal endothelial (SCE) cells.
• To elucidate the role of VEGF receptors in mediating these effects.

Main Methods:

• Human recombinant VEGF121 and VEGF165 were utilized.
• Trabecular meshwork (TM) and Schlemm's canal endothelial (SCE) cells were isolated from cynomolgus monkey eyes.
• Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine VEGF receptor mRNA expression.
• Transendothelial electrical resistance (TEER) was measured to assess cell monolayer permeability.
• Outflow facility was measured in perfused porcine anterior segment organ cultures.

Main Results:

• TM and SCE cells expressed four types of VEGF-A receptor mRNAs.
• VEGF121 significantly reduced the TEER of SCE cells, indicating increased permeability (P = 0.0001).
• VEGF121 treatment significantly increased the outflow facility in porcine anterior segment organ cultures (P = 0.013).
• A selective VEGFR2 inhibitor (Ki8751) blocked the effect of VEGF121 on SCE cell permeability.

Conclusions:

• VEGF-A significantly impacts the permeability of Schlemm's canal endothelial cells.
• VEGF-A increases aqueous humor outflow facility.
• These effects are mediated through the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2).
• VEGF-A may play a regulatory role in the conventional aqueous outflow pathway via SCE cells and VEGFR2.