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.
摘要:
硫芥子气(SM)诱导的眼部损伤的特征是急性炎症反应,可能会变成慢性或进入潜伏期,病理延迟。本研究旨在评估齐夫-阿柏西普和阿柏西普预防和改善角膜新生血管形成(NV)的疗效。分别,在兔子模型中化学眼睛暴露于SM蒸气之后。在兔的右眼中诱导化学SM眼部损伤。暴露后2小时或9天单次施用ziv-阿柏西普。在SM蒸气暴露后4周和随后用0.1%地塞米松进行的初始1周治疗之后,在眼部制剂中施用单一结膜下阿柏西普治疗。暴露后5-12周进行临床监测,并拍摄数字角膜照片以评估NV的程度。将兔安乐死,并处理角膜用于组织学评估。暴露后2h和9天接受ziv-aflibercept治疗可中度降低损伤严重程度,并部分延迟或预防角膜NV。暴露后4周的Aflibercept应用显着降低了NV的程度,持续了8周。组织学证实了该组中现有角膜NV的显着降低。这些结果揭示了VEGF陷阱对改善现有NV而不是预防NV发展的强大抗血管生成功效。揭示了这种治疗减轻角膜NV的能力。