Spinster 2 (Spns2) is a transporter that pumps sphingosine-1-phosphate (S1P), a bioactive lipid mediator synthesized in the cytoplasm, out of cells into the inter cellular space. S1P is a signal that modulates cellular behavior during embryonic development, inflammation and tissue repair, etc. A Spns2-null (KO) mouse is born with failure of eyelid closure (eyelid-open-at birth; EOB) and develop corneal fibrosis in adulthood. It remains elusive whether corneal lesion is caused by exposure to keratitis (lagophthalmos) of EOB phenotype or the loss of Spns2 directly perturbs the corneal tissue morphogenesis and intra-eyelid structures. Therefore, we investigated differences between the cornea and ocular adnexa morphogenesis in KO and wild-type (WT) embryos and adults as well.

The loss of Spns2 perturbs cornea morphogenesis during embryonic development as early as E16.5 besides EOB phenotype. Histology showed that the corneal stroma was thinner with less extracellular matrix accumulation, e.g., collagen and keratocan in the KO mouse. Epithelial stratification, expression of keratin 12 and formation of desmosomes and hemidesmosomes were also perturbed in these KO corneas. Lacking Spns2 impaired morphogenesis of the Meibomian glands and of orbicularis oculi muscles. KO glands were labeled for ELOVL4 and PPARγ and were Oil-Red O-positive, suggesting KO acinar cells possessed functionality as the glands.

This is the first report on the roles of Spns2 in corneal and Meibomian gland morphogenesis. Corneal tissue destruction in an adult KO mouse might be due to not only lagophthalmos but also to an impaired morphogenesis of cornea, Meibomian glands, and orbicularis oculi muscle.

Spinster 2 (Spns2) 是一种转运蛋白，可将鞘氨醇-1-磷酸 (S1P)（一种在细胞质中合成的生物活性脂质介质）泵出细胞，进入细胞间隙。S1P 是一种在胚胎发育、炎症和组织修复等过程中调节细胞行为的信号。Spns2-null (KO) 小鼠出生时眼睑闭合失败（eyelid -open-at birth；EOB），成年期出现角膜纤维化. 目前尚不清楚角膜损伤是由暴露于EOB 表型角膜炎(lagophthalmos) 还是 Spns2 的缺失直接扰乱角膜组织形态发生和眼睑内结构引起的。因此，我们研究了角膜和眼睛之间的差异KO 和野生型 (WT) 胚胎和成人的附件形态发生。

除了 EOB 表型外，早在 E16.5 胚胎发育过程中，Spns2 的缺失就会扰乱角膜形态发生。组织学显示角膜基质较薄，细胞外基质积累较少，例如 KO 小鼠中的胶原蛋白和角质形成细胞。在这些 KO 角膜中，上皮分层、角蛋白 12的表达以及桥粒和半桥粒的形成也受到干扰。缺乏 Spns2 会损害睑板腺和眼轮匝肌的形态发生。KO 腺体被标记为 ELOVL4 和 PPARγ，并且呈油红 O 阳性，表明 KO腺泡细胞具有与腺体相同的功能。

这是关于 Spns2 在角膜和睑板腺形态发生中的作用的第一份报告。成年 KO 小鼠的角膜组织破坏可能不仅是由于眼球突出，还可能是由于角膜、睑板腺和眼轮匝肌的形态发生受损。