Program in Craniofacial Biology, Department of Cell & Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Herbert Wertheim School of Optometry and Vision Science, University of California, Berkeley, Oakland, CA 94720, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell Rep. 2022 Aug 30;40(9):111307. doi: 10.1016/j.celrep.2022.111307.
Corneal architecture is essential for vision and is greatly perturbed by the absence of tears due to the highly prevalent disorder dry eye. With no regenerative therapies available, pathological alterations of the ocular surface in response to dryness, including persistent epithelial defects and poor wound healing, result in lifelong morbidity. Here, using a mouse model of aqueous-deficient dry eye, we reveal that topical application of the synthetic tear protein Lacripep reverses the pathological outcomes of dry eye through restoring the extensive network of corneal nerves that are essential for tear secretion, barrier function, epithelial homeostasis, and wound healing. Intriguingly, the restorative effects of Lacripep occur despite extensive immune cell infiltration, suggesting tissue reinnervation and regeneration can be achieved under chronic inflammatory conditions. In summary, our data highlight Lacripep as a first-in-class regenerative therapy for returning the cornea to a near homeostatic state in individuals who suffer from dry eye.
角膜结构对于视觉至关重要，但由于高度流行的干眼症导致缺乏眼泪，其结构会受到极大干扰。由于没有再生疗法，眼部表面对干燥的病理改变，包括持续的上皮缺损和愈合不良，导致终身发病。在这里，我们使用一种缺乏水样液的干眼症小鼠模型，揭示了局部应用合成泪液蛋白 Lacripep 通过恢复对泪液分泌、屏障功能、上皮稳态和伤口愈合至关重要的广泛角膜神经网络，逆转干眼症的病理结果。有趣的是，Lacripep 的修复作用发生在广泛的免疫细胞浸润的情况下，这表明在慢性炎症条件下可以实现组织再神经支配和再生。总之，我们的数据强调 Lacripep 是一种一流的再生疗法，可以使干眼症患者的角膜恢复到接近生理平衡的状态。
