Abstract：
The conjunctiva is a non-keratinized, stratified columnar epithelium with characteristics different from the cornea and eyelid epidermis. From development to adulthood, a distinguishing feature of ocular versus epidermal epithelia is the expression of the master regulator PAX6. A conditionally immortalized conjunctival epithelial cell line (iHCjEC) devoid of stromal or immune cells established in our laboratory spontaneously manifested epidermal metaplasia and upregulated expression of the keratinization-related genes SPRR1A/B and the epidermal cytokeratins KRT1 and KRT10 at the expense of the conjunctival trait. In addition, iHCjEC indicated a significant decrease in PAX6 expression. Dry eye syndrome (DES) and severe ocular surface diseases, such as Sjögren\'s syndrome and Stevens-Johnson syndrome, cause the keratinization of the entire ocular surface epithelia. We used iHCjECs as a conjunctiva epidermal metaplasia model to test PAX6, serum, and glucocorticoid interventions. Reintroducing PAX6 to iHCjECs resulted in upregulating genes related to cell adhesion and tight junctions, including MIR200CHG and CLDN1. The administration of glucocorticoids or serum resulted in the downregulation of epidermal genes (DSG1, SPRR1A/B, and KRT1) and partially corrected epidermal metaplasia. Our results using an isolated conjunctival epidermal metaplasia model point toward the possibility of rationally \"repurposing\" clinical interventions, such as glucocorticoid, serum, or PAX6 administration, for treating epidermal metaplasia of the conjunctiva.
摘要：
结膜是非角化的，具有不同于角膜和眼睑表皮特征的复层柱状上皮。从发育到成年，眼上皮与表皮上皮的区别特征是主调节因子PAX6的表达。在我们的实验室中建立的无基质或免疫细胞的条件永生化结膜上皮细胞系（iHCjEC）自发表现为表皮化生，并以牺牲为代价上调角质化相关基因SPRR1A/B和表皮细胞角蛋白KRT1和KRT10的表达结膜性状。此外,iHCjEC表明PAX6表达显著降低。干眼综合征（DES）和严重的眼表疾病，如Sjögren综合征和Stevens-Johnson综合征,引起整个眼表上皮的角质化。我们使用iHCjECs作为结膜表皮上皮化生模型来测试PAX6，血清，和糖皮质激素干预。将PAX6重新引入iHCjECs导致与细胞粘附和紧密连接相关的基因上调，包括MIR200CHG和CLDN1。糖皮质激素或血清的给药导致表皮基因的下调（DSG1，SPRR1A/B，和KRT1）和部分矫正的表皮上皮化生。我们使用孤立的结膜表皮上皮化生模型的结果指向合理的“再利用”临床干预的可能性，如糖皮质激素，血清,或PAX6管理，用于治疗结膜表皮化生。
