Delafontaine Marie, Panfil Claudia, Spöler Felix, Kray Stefan, Burgher François, Mathieu Laurence, Blomet Joël, Schrage Norbert F, Tambourgi Denise V
Prevor Laboratory, Valmondois, France; Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
Aachen Centre of Technology Transfer in Ophthalmology, Aachen, Germany.
Toxicon. 2018 Aug;150:253-260. doi: 10.1016/j.toxicon.2018.06.061. Epub 2018 Jun 8.
Snakes belonging to the genus Naja (Elapid family), also known as "spitting cobras", can spit venom towards the eyes of the predator as a defensive strategy, causing painful and potentially blinding ocular envenoming. Venom ophthalmia is characterized by pain, hyperemia, blepharitis, blepharospasm and corneal erosions. Elapid venom ophthalmia is not well documented and no specific treatment exists. Furthermore, accidental ejection of venom by non-spitting vipers, as Bothrops, also occurs. The Ex vivo Eye Irritation Test model (EVEIT) has enabled important progress in the knowledge of chemical ocular burns. Considering the lack of experimental animal model, we adapted the EVEIT to study venom ophthalmia mechanisms. Ex vivo rabbit corneas were exposed to venoms from spitting (Naja mossambica, Naja nigricollis) and non-spitting (Naja naja, Bothrops jararaca and Bothrops lanceolatus) snakes, and rinsed or not with water. The corneal thickness and the depth of damage were assessed using high-resolution optical coherence tomography (HR-OCT) imaging and histological analysis. All Naja venoms induced significant corneal edema, collagen structure disorganization and epithelial necrosis. Corneas envenomed by African N. mossambica and N. nigricollis venoms were completely opaque. Opacification was not observed in corneas treated with venoms from non-spitting snakes, such as the Asian cobra, N. naja, and the vipers, B. jararaca and B. lanceolatus. Moreover, Bothrops venoms were able to damage the epithelium and cause collagen structure disorganization, but not edema. Immediate water rinsing improved corneal status, though damage and edema could still be observed. In conclusion, the present study shows that the EVEIT model was successfully adapted to set a new experimental ex vivo animal model of ophthalmia, caused by snake venoms, which will enable to explore new therapies for venom ophthalmia.
眼镜蛇属（眼镜蛇科）的蛇类，也被称为“喷毒眼镜蛇”，作为一种防御策略，它们可以向捕食者的眼睛喷射毒液，导致疼痛且可能致盲的眼部中毒。毒液性眼炎的特征是疼痛、充血、睑缘炎、睑痉挛和角膜糜烂。眼镜蛇科毒液性眼炎的记录并不充分，也没有特效治疗方法。此外，非喷毒蝰蛇（如矛头蝮属）意外喷射毒液的情况也会发生。体外眼刺激试验模型（EVEIT）在化学性眼烧伤的研究方面取得了重要进展。鉴于缺乏实验动物模型，我们对EVEIT进行了改进，以研究毒液性眼炎的机制。将离体兔角膜暴露于喷毒蛇（莫桑比克眼镜蛇、黑颈眼镜蛇）和非喷毒蛇（眼镜王蛇、巴西矛头蝮和三色矛头蝮）的毒液中，并用水冲洗或不冲洗。使用高分辨率光学相干断层扫描（HR-OCT）成像和组织学分析评估角膜厚度和损伤深度。所有眼镜蛇毒液均引起明显的角膜水肿、胶原结构紊乱和上皮坏死。被非洲莫桑比克眼镜蛇和黑颈眼镜蛇毒液毒害的角膜完全不透明。在用非喷毒蛇（如亚洲眼镜蛇眼镜王蛇以及蝰蛇巴西矛头蝮和三色矛头蝮）的毒液处理的角膜中未观察到浑浊。此外，矛头蝮属毒液能够损伤上皮并导致胶原结构紊乱，但不会引起水肿。立即用水冲洗可改善角膜状况，不过仍可观察到损伤和水肿。总之，本研究表明EVEIT模型成功地被改进，建立了一种新的由蛇毒引起的体外实验性眼炎动物模型，这将有助于探索毒液性眼炎的新疗法。
