Nintedanib Inhibits VEGF-Induced Neovascularization in Human Conjunctival Vascular Endothelial Cells

Area of Science:

• Ophthalmology
• Cell Biology
• Pharmacology

Background:

• Filtering bleb scarring post-glaucoma surgery is linked to conjunctival vascularization and fibroblasts.
• Nintedanib is known to inhibit fibroblast to myofibroblast transformation, mitigating scar formation.

Purpose of the Study:

• To investigate nintedanib's effect on vascular endothelial growth factor (VEGF)-induced neovascularization in human conjunctival vascular endothelial cells.
• To elucidate the molecular mechanisms underlying nintedanib's action on these cells.

Main Methods:

• Primary human conjunctival vascular endothelial cells were treated with VEGF alone or with nintedanib.
• Cell proliferation, migration, and tube formation were assessed using cell counting kit-8, scratch assays, and tube formation assays.
• Western blotting was used to measure phosphorylation levels of ERK1/2 and JNK.

Main Results:

• VEGF significantly increased human conjunctival vascular endothelial cell proliferation.
• Nintedanib inhibited VEGF-induced proliferation, suppressed cell migration (P < 0.0001), and reduced vascularization (P < 0.01).
• Nintedanib decreased phosphorylation of ERK1/2 (P < 0.01) and JNK (P < 0.001).

Conclusions:

• Nintedanib inhibits proliferation, migration, and neovascularization of human conjunctival vascular endothelial cells.
• The drug downregulates p-ERK and p-JNK expression within the MAPK pathway.
• These findings suggest nintedanib's potential in managing glaucoma surgery complications.