The use of aflibercept (VEGF trap) in mitigating sulfur mustard-induced corneal neovascularization in a rabbit model

Ariel Gore; Tamar Kadar; Maayan Cohen; Hila Gutman; Rellie Gez; Shlomit Dachir; Vered Horwitz

doi:10.1016/j.toxrep.2023.01.013

The use of aflibercept (VEGF trap) in mitigating sulfur mustard-induced corneal neovascularization in a rabbit model

Toxicol Rep. 2023 Jan 27:10:206-215. doi: 10.1016/j.toxrep.2023.01.013. eCollection 2023.

Authors

Ariel Gore¹, Tamar Kadar¹, Maayan Cohen¹, Hila Gutman¹, Rellie Gez¹, Shlomit Dachir¹, Vered Horwitz¹

Affiliation

¹ Department. of Pharmacology, Israel Institute for Biological Research, Ness Ziona 74100, Israel.

Abstract

Sulfur mustard (SM)-induced ocular injury is characterized by an acute inflammatory response that may become chronic or enter a latent phase with delayed pathology. This study aimed to evaluate the efficacy of ziv-aflibercept and aflibercept in preventing and ameliorating corneal neovascularization (NV), respectively, following chemical eye exposure to SM vapor in a rabbit model. Chemical SM ocular insult was induced in the right eye of rabbits. A single application of ziv-aflibercept was administered 2 h or 9 days post-exposure. A single subconjunctival aflibercept treatment in an ocular formulation was administered 4 weeks after SM vapor exposure and subsequent to an initial 1-week treatment with 0.1 % dexamethasone. Clinical monitoring was performed 5-12 weeks post-exposure, and digital corneal pictures were taken to assess the extent of NV. The rabbits were euthanized and the corneas were processed for histological assessment. Treatment with ziv-aflibercept 2 h and 9 days post-exposure moderately reduced insult severity and partially delayed or prevented corneal NV. Aflibercept application 4 weeks post-exposure significantly reduced the extent of NV for 8 weeks. The substantial decrease in existing corneal NV in this group was confirmed by histology. These results reveal the powerful anti-angiogenic efficacy of the VEGF-trap for ameliorating existing NV as opposed to preventing NV development, revealing the ability of this treatment to mitigate corneal NV.

Keywords: ANOVA, analysis of variance; Aflibercept; NV, neovascularization; NZW, New Zealand White rabbit; Neovascularization; Ocular chemical insult; Ocular surface; PlGF, placental growth factor; SM, sulfur mustard; Sulfur mustard; TGF-β, transforming growth factor beta; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor.