Glaudo Markus, Panfil Claudia, Schrage Norbert F
Aachen Centre of Technology Transfer in Ophthalmology, (ACTO e. V.) Karlsburgweg 9, 52070 Aachen, Germany.
Toxicol Rep. 2021 Jun 8;8:1200-1206. doi: 10.1016/j.toxrep.2021.06.005. eCollection 2021.
Live-animal-free ocular toxicity models and tests are a necessity in multiple branches of medicine, industry and science. Corneal models with adjustable ranges of injury severities do not exist. In this work, a novel and precise and dose - response method to induce and observe corneal chemical burns has been established.
The EVEIT (Ex Vivo Eye Irritation Test) is based on an corneal organ model for rabbit corneas from food industry. Further, a highly precise three - axis workstation has been employed to apply liquid corrosive, sodium hydroxide (NaOH), droplets in a nanolitre (nL) range onto the corneal surface. Optical Coherence Tomography (OCT) has been used to observe and quantify the elicited changes in the corneal layers.
The speed and intervals of single nanodroplet application played a crucial role in the extent of the corneal changes. Similar total volumes applied at low frequencies elicited deep and extensive changes in the corneal layers whereas high application frequencies elicited comparatively superficial changes. Increasing NaOH concentrations effected measurably increasing corneal changes. Increasing the volume of applied NaOH also showed an increase in corneal changes.
OCT imaging proved to be effective in observing, documenting and quantifying the changes in the corneal layers. The model, in conjunction with the novel application method was able to induce and display distinctive and consistent correlations between NaOH volume, concentration and elicited corneal changes. This ocular chemical burn model provides a consistent basis for pharmaceutical and toxicological experiments and investigations into corneal chemical burn mechanisms and treatment.
无活体动物的眼毒性模型和测试在医学、工业和科学的多个分支中都是必要的。不存在损伤严重程度范围可调节的角膜模型。在这项工作中,建立了一种新颖、精确的剂量反应方法来诱导和观察角膜化学烧伤。
EVEIT(离体眼刺激试验)基于食品工业中兔角膜的角膜器官模型。此外,还使用了高精度的三轴工作站将纳升(nL)范围内的液体腐蚀性物质氢氧化钠(NaOH)液滴施加到角膜表面。光学相干断层扫描(OCT)已被用于观察和量化角膜层中引发的变化。
单个纳滴施加的速度和间隔对角膜变化的程度起着关键作用。在低频下施加相似的总体积会引起角膜层的深度和广泛变化,而高频施加则引起相对较浅的变化。增加NaOH浓度会导致角膜变化明显增加。增加NaOH的施加体积也显示角膜变化增加。
OCT成像被证明在观察、记录和量化角膜层的变化方面是有效的。该模型与新颖的施加方法相结合,能够诱导并显示NaOH体积、浓度与引发的角膜变化之间独特且一致的相关性。这种眼化学烧伤模型为药物和毒理学实验以及角膜化学烧伤机制和治疗的研究提供了一致的基础。