Ocular surface pathogenesis associated with precocious eyelid opening and necrotic autologous tissue in mouse with disruption of Prickle 1 gene
Ocular surface pathogenesis associated with precocious eyelid opening and necrotic autologous tissue in mouse with disruption of Prickle 1 gene
复制标题
Prickle 1 基因破坏小鼠眼表发病机制与早熟眼睑张开和坏死自体组织相关
DOI：
10.1016/j.exer.2018.12.012
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发表时间：
2019-03-01
影响因子：
3.4
通讯作者：
Liu, Chunqiao
中科院分区：
文献类型：
--
作者：
Guo, Dianlei;Li, Mengke;Liu, Chunqiao
眼表疾病是眼部疾病的主要类型之一。不同的病因会引发不同的眼表病理反应。我们之前报道过，去除 Prickle 1 的基因工程小鼠表现出眼睑过早张开，并伴有随后的角膜发育不良。目前的研究旨在表征 Prickle 1 突变小鼠眼睑早熟相关的分子特征和眼部病理学的直接原因。 Prickle 1突变小鼠表现出一系列眼表病理，包括细胞增殖、细胞命运转变和炎症浸润，与眼睑过早张开的时间相一致。与 Prickle 1 突变体相比，强制打开野生型小鼠的眼睑不会引起角膜病理。发现与受损角膜相关的坏死组织碎片。对突变角膜的 RNAseq 分析揭示了一系列涉及免疫反应和癌症的皮肤病所共有的表达谱。综上所述，数据表明坏死的眼睑碎片在 Prickle 1 突变小鼠的眼部发病机制中起着重要作用，这可能代表一种由受损自体组织引起的非感染性角结膜炎。此外，Prickle 1 突变角膜发病机制可能为其他类型的上皮发病机制提供分子见解。
Ocular surface disease is one major type of eye diseases. Different etiologies trigger distinct pathological responses of the ocular surface. We previously reported that genetically engineered mice with ablation of Prickle 1 manifested precocious eyelid opening with ensuing cornea dysplasia. The current study aimed to characterize the molecular traits and the direct cause of ocular pathology associated with precocious eyelid opening in the Prickle 1 mutant mouse. Prickle 1 mutant mice exhibited a slew of ocular surface pathology including cell proliferation, cell fate transformation and inflammatory infiltration coinciding with the timing of the precocious eyelid opening. Forced eyelid opening in wild type mice did not induce cornea pathology comparable to that of the Prickle 1 mutants. Necrotic tissue debris was found associated with the lesioned cornea. RNAseq analysis of the mutant cornea revealed an expression profile shared by a range of dermatological diseases involving immune responses and cancer. Taken together, the data suggest that the necrotic eyelid debris plays an important role in ocular pathogenesis of the Prickle 1 mutant mouse, which may represent a type of non-infectious keratoconjunctivitis caused by damaged autologous tissues. Additionally, Prickle 1 mutant cornea pathogenesis may offer molecular insights into other types of epithelial pathogenesis.