角膜缘干细胞缺乏动物模型建立方法研究进展

Review of methods for establishing limbal stem cell deficiency in animal model

角膜缘干细胞缺乏(LSCD)是眼科常见疾病,严重的LSCD是角膜病致盲的主要原因之一。LSCD新疗法的探索仍是当今研究的热点。建立LSCD动物模型有助于更深入了解LSCD的发病机制以及评估治疗方法的有效性。目前,LSCD建模的主要方式有机械法、灼烧法、化学法、化学+手术法及基因敲减法。机械法成熟可靠,应用广泛,但可能会引起严重的机械损伤。其中,使用旋转毛刺工具造模损伤均匀且创伤小,但对于工具的使用需要一定的经验积累。灼烧法造模表型稳定,但操作复杂可控性差。化学法造模快速简单,病因与临床病例的吻合度较高,但损伤的深度及范围不可控。化学+手术法角膜表面光滑平整,但易导致角膜中央与角膜缘厚度不一致,影响新生血管生长。基因敲减法复杂且动物饲养困难,应用较少。虽然造模方法众多,但各研究中的造模质量参差不齐。因此,建立可靠、成功率高的LSCD动物模型十分必要。本文就近年来常用LSCD动物模型的建立方法及优缺点进行综述,以期为后续构建合适模型提供借鉴。

Limbal stem cell deficiency(LSCD)is a common ocular surface disease.Severe LSCD can cause irreversible vision loss and the only effective treatment for severe LSCD is keratoplasty,which is limited by the number of donors.Exploring new effective treatments in lieu of keratoplasty remains a hot topic in current research.Since new treatments need to be critically evaluated in reliable animal models that reflect the pathological mechanisms of human LSCD,the establishment of an appropriate animal model is crucial in any experiment.Up to now,the main modeling methods for LSCD are mechanical method,thermal injury,chemical method,chemical method combined with surgery,and gene knock-down.Mechanical method is mature,reliable and widely used,but it can cause serious mechanical damage.Rotate burr tool could be the best mechanical method because of uniform damage and the small trauma,but it requires accumulation of experience.Cornea suffered from thermal injury performs stable,but the operation is complicated and uncontrollable.Chemical method is quick and simple,and the etiology is highly consistent with clinical cases,but the depth and extent of injury are uncontrollable.The chemical method combined with surgery could ensure the smoothness and flattening of the corneal surface,but the thickness of the central cornea and the limbus may be inconsistent,which affects neovascularization.The gene knockdown method is not widely used because of its complicated operations.Although there are different types of methods,the quality of modeling in different studies is not consistent.Therefore,selecting a reliable and efficient animal model of LSCD is not convenient for researchers.This review discussed current methods to establish LSCD model,including their advantages and disadvantages,therefore to provide inspiration for future model improvement.