A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.
A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.
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DOI：
10.1016/j.celrep.2022.111307
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发表时间：
2022-08-30
期刊：
影响因子：
8.8
通讯作者：
Knox, Sarah M.
中科院分区：
文献类型：
--
作者：
Efraim, Yael;Chen, Feeling Yu Ting;Cheong, Ka Neng;Gaylord, Eliza A.;McNamara, Nancy A.;Knox, Sarah M.
角膜结构对于视觉是必不可少的，并且由于高度流行的干眼病症而不流泪而受到极大的干扰。由于没有可用的再生疗法，眼表响应于干燥的病理学改变，包括持续的上皮缺陷和不良的伤口愈合，导致终身发病。在这里，使用缺水性干眼症的小鼠模型，我们揭示了合成泪液蛋白Lacripep的局部应用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的角膜神经网络来逆转干眼症的病理结果。有趣的是，尽管有广泛的免疫细胞浸润，Lacripep的恢复作用仍然存在，这表明在慢性炎症条件下可以实现组织神经再支配和再生。总之，我们的数据突出了Lacripep作为一流的再生疗法，用于使患有干眼症的个体的角膜恢复到接近稳态的状态。目前，对于干眼引起的眼部病变没有再生治疗。Efraim等人证明了合成泪液肽Lacripep作为一种再生疗法，能够通过在慢性炎症存在的情况下促进神经再生，将受损的、功能失调的眼表面恢复到接近稳态的状态。
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 life-long 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. Currently, there are no regenerative treatments for ocular pathologies due to dry eye. Efraim et al. demonstrate the synthetic tear peptide Lacripep as a regenerative therapy capable of restoring the damaged, dysfunctional ocular surface to a near homeostatic state through promoting nerve regeneration in the presence of chronic inflammation.
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影响因子：
5.6
作者：
Chen FY;Gaylord E;McNamara N;Knox S
通讯作者：
Knox S
影响因子：
3.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Rompolas P
影响因子：
5.2
作者：
Di Girolamo, N.;Bobba, S.;Lyons, J. G.
通讯作者：
Lyons, J. G.
DOI：
10.1073/pnas.1715272116
发表时间：
2019-07-16
影响因子：
11.1
作者：
Boonekamp, Kim E.;Kretzschmar, Kai;Clevers, Hans
通讯作者：
Clevers, Hans