Lacripep promotes corneal regeneration in autoimmune mediated dry eye disease

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. Comparative analysis of gene expression between wild type, untreated Aire KO (dry eye disease) , Aire KO treated with PBS, and Aire KO treated with 4uM lacripep whole corneas at day 7 of treatment (6 wk of age).

角膜结构对视力至关重要，而高发的干眼症引发的泪液缺失会严重扰乱该结构。目前尚无可用的再生治疗手段，干燥应激引发的眼表病理改变（包括持续性上皮缺损与创伤愈合不良）会导致终身患病负担。本研究利用水液缺乏型干眼症小鼠模型，发现局部应用合成泪液蛋白lacripep，可通过修复对泪液分泌、屏障功能、上皮稳态及创伤愈合均不可或缺的广泛角膜神经网络，逆转干眼症的病理结局。有趣的是，即便存在大量免疫细胞浸润，lacripep仍可发挥修复作用，这表明在慢性炎症状态下仍可实现组织再支配与再生。综上，本研究数据证实lacripep可作为首款同类首创的再生治疗策略，帮助干眼症患者的角膜恢复至近乎稳态的状态。本研究针对治疗第7天（小鼠6周龄）的全角膜样本开展基因表达对比分析，样本分组包括野生型组、未处理的Aire基因敲除（Aire KO，干眼症模型）组、经磷酸盐缓冲液（PBS）处理的Aire KO组，以及经4μM lacripep处理的Aire KO组。