Effects of Dual Inhibition of VEGF-A and Angpt-2 on Angiogenesis and Lymphangiogenesis in an Alkali-Induced Corneal Injury Model

Corneal neovascularization (CNV) is frequently observed after various corneal injuries and corneal transplantation, leading to impairment of corneal transparency. Lymphangiogenesis and the inflammatory response often accompany CNV. Chemical injury is one of the most common causes of CNV, and alkali injury has been widely used as an animal model of this pathological state. We examined the effects of subconjunctival injection of an anti-VEGFA antibody (anti-VEGFA_ab), anti-ANGPT2 antibody (anti-ANGPT2_ab), and bispecific antibody against VEGFA and ANGPT2 (BsAb) in CNV using the alkali injury mouse model. The pathological indexes were examined using anterior segment optical coherence tomography (OCT) and whole-mount immunostaining, and gene expression patterns were examined using RT-qPCR. Treatment with anti-VEGFA_ab, anti-ANGPT2_ab, or BsAb did not affect the swelled thickness of the cornea; however, angiogenesis, but not lymphangiogenesis, was hampered by the treatment of either one of the antibodies. We observed an increase in the mRNA levels of Vegfa, Angpt2, Il1b, and Cx3cr1 following alkali injury. The administration of BsAb suppressed the induction of Vegfa and Cx3cr1. Additionally, BsAb treatment enhanced the mRNA levels of Angpt1 in this model. This study demonstrates the potential of dual VEGFA and ANGPT2 inhibition as a therapeutic strategy for CNV.