Schuh JoAnn C L, Holve Dana L, Mundwiler Karen E
JCL Schuh, PLLC, Bainbridge Island, WA, USA.
486251Biological Test Center, Irvine, CA, USA.
Toxicol Pathol. 2021 Apr;49(3):555-568. doi: 10.1177/0192623320968092. Epub 2020 Dec 8.
The International Committee for Classification of Corneal Dystrophies (IC3D) categorized corneal dystrophies in humans using anatomic, genotypic, and clinicopathologic phenotypic features. Relative to the IC3D classification, a review of the veterinary literature confirmed that corneal dystrophy is imprecisely applied to any corneal opacity and to multiple poorly characterized histologic abnormalities of the cornea in animals. True corneal dystrophy occurs in mice with targeted mutations and spontaneously in pet dogs and cats and in Dutch belted (DB) rabbits, but these instances lack complete phenotyping or genotyping. Corneal dystrophy in DB rabbits can be an important confounding finding in ocular toxicology studies but has only been described once. Therefore, the ophthalmology and pathology of corneal dystrophy in 13 DB rabbits were characterized to determine whether the findings were consistent with or a possible model of any corneal dystrophy subtypes in humans. Slit lamp and optical coherence tomography (OCT) imaging were used to characterize corneal dystrophy over 4 months in young DB rabbits. The hyperechoic OCT changes correlated with light microscopic findings in the anterior stroma, consisting of highly disordered collagen fibers and enlarged keratocytes. Histochemical stains did not reveal abnormal deposits. Small clusters of 8 to 16 nm diameter curly fibers identified by transmission electron microscopy were consistent with Thiel-Behnke (TBCD) subtype of epithelial-stromal transforming growth factor β-induced dystrophies. Sporadic corneal dystrophy in DB rabbits appears to be a potential animal model of TBCD, but genotypic characterization will be required to confirm this categorization.
国际角膜营养不良分类委员会(IC3D)利用解剖学、基因型和临床病理表型特征对人类角膜营养不良进行分类。相对于IC3D分类,对兽医文献的回顾证实,角膜营养不良在动物中被不精确地应用于任何角膜混浊以及角膜的多种特征不明确的组织学异常。真正的角膜营养不良发生在具有靶向突变的小鼠中,也自发出现于宠物狗和猫以及荷兰带兔(DB兔)中,但这些病例缺乏完整的表型分析或基因分型。DB兔的角膜营养不良在眼毒理学研究中可能是一个重要的混淆发现,但仅被描述过一次。因此,对13只DB兔角膜营养不良的眼科和病理学特征进行了研究,以确定这些发现是否与人类角膜营养不良亚型一致或是否可能是其模型。在幼年DB兔中,使用裂隙灯和光学相干断层扫描(OCT)成像在4个月内对角膜营养不良进行特征分析。OCT的高回声变化与前基质层的光学显微镜检查结果相关,前基质层由高度紊乱的胶原纤维和增大的角膜细胞组成。组织化学染色未发现异常沉积物。通过透射电子显微镜鉴定的直径为8至16 nm的小卷曲纤维簇与上皮 - 基质转化生长因子β诱导的营养不良的蒂尔 - 贝恩克(TBCD)亚型一致。DB兔中的散发性角膜营养不良似乎是TBCD的潜在动物模型,但需要进行基因分型来证实这一分类。