Abstract
Purpose :
VEGF Trap is a recombinant chimeric soluble receptor containing ligand-binding elements taken from the extracellular components of human VEGF receptors 1 and 2 fused to the Fc portion of IgG1 and it binds all VEGF-A, VEGF-B and PIGF with high affinity (Holash et al., 2002). VEGF Trap-Eye (aflibercept) has been approved for intravitreal delivery to treat several clinical conditions with retinal and choroidal pathological neovascularization. Our previous study of topical administration of VEGF Trap significantly inhibited CoNV in mice (Liu Y, et al. ARVO 2008). The present study investigates the effects of topical VEGF Trap on the development of neovascularization following corneal suture injury in rabbit.
Methods :
18 adult male New Zealand White rabbits were used for this study. The published method describing CoNV by suture placement in rabbit [Perez-Santonja et al., 2010] was adapted to our model. In brief, five 8-0 interrupted silk sutures were placed at mid-stromal depth in the upper cornea on day 0. VEGF Trap applied as a 25uL drop was topically administered three times a day (9:00am, 1:00pm, and 5:00pm) at the concentrations of 100, 50, 25 and 10 mg/mL, respectively in each group (n=3 eyes/3 rabbits) beginning from Day 1 after suture placement. Control animals received eye drops of Vehicle or hFc solution. 12 days post suture injury, corneal photographs were taken using a digital camera, then the eyeballs were collected for histological analysis. Areas of corneal neovessels were measured using Photoshop masked for the treatment groups. Corneal thickness was quantified, and infiltration of leukocytes was evaluated in cross-sections stained with H&E and immunohistochemistry for CD45.
Results :
Topical administration of VEGF Trap inhibited rabbit CoNV by 97.4%, 84.0%, 82.4% and 80.0% at the concentrations of 100, 50, 25,10 mg/mL, respectively compared to Vehicle Control group, and by 96.2%, 76.5%, 74.1% and 70.6%, respectively compared to hFc control group. Topical VEGF Trap treatment also markedly reduced inflammation induced by corneal injury.
Conclusions :
This study demonstrates that topical application of VEGF Trap effectively inhibits CoNV and inflammation following suture injury in rabbit.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.