Gore Ariel, Kadar Tamar, Cohen Maayan, Gutman Hila, Gez Rellie, Dachir Shlomit, Horwitz Vered
Department. of Pharmacology, Israel Institute for Biological Research, Ness Ziona 74100, Israel.
Toxicol Rep. 2023 Jan 27;10:206-215. doi: 10.1016/j.toxrep.2023.01.013. eCollection 2023.
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.
硫芥（SM）所致眼损伤的特征是急性炎症反应，该反应可能会转为慢性或进入潜伏期并伴有延迟性病理变化。本研究旨在评估在兔模型中，化学性眼部暴露于SM蒸气后，阿柏西普眼内注射溶液和阿柏西普分别在预防和改善角膜新生血管（NV）方面的疗效。在兔的右眼诱导化学性SM眼部损伤。暴露后2小时或9天单次应用阿柏西普眼内注射溶液。在SM蒸气暴露后4周以及在最初用0.1%地塞米松治疗1周后，对眼部制剂进行单次结膜下阿柏西普治疗。在暴露后5至12周进行临床监测，并拍摄角膜数码照片以评估NV的程度。对兔实施安乐死后，对角膜进行组织学评估。暴露后2小时和9天用阿柏西普眼内注射溶液治疗可适度降低损伤严重程度，并部分延迟或预防角膜NV。暴露后4周应用阿柏西普可在8周内显著降低NV的程度。组织学证实该组中现有角膜NV大幅减少。这些结果揭示了VEGF陷阱在改善现有NV而非预防NV发展方面强大的抗血管生成功效，表明这种治疗方法有减轻角膜NV的能力。
