Efraim Yael, Chen Feeling Yu Ting, Niknezhad Seyyed Vahid, Pham Dylan, Cheong Ka Neng, An Luye, Sinada Hanan, McNamara Nancy A, Knox Sarah M
Program in Craniofacial Biology, Department of Cell & Tissue Biology, University of California San Francisco; San Francisco, CA 94143, USA.
School of Optometry and Vision Science Graduate Program, University of California, Berkeley; Oakland, CA 94720, USA.
bioRxiv. 2024 Dec 3:2024.11.29.626078. doi: 10.1101/2024.11.29.626078.
Corneal lubrication is the most common treatment for relieving the signs and symptoms of dry eye and is considered to be largely palliative with no regenerative functions. Here we challenge this notion by demonstrating that wetting the desiccated cornea of an aqueous-deficient mouse model with the simplest form of lubrication, a saline-based solution, is sufficient to rescue the severely disrupted collagen-rich architecture of the stroma, the largest corneal compartment that is essential to transparency and vision. At the single cell level we show that stromal keratocytes responsible for maintaining stromal integrity are converted from an inflammatory state into unique reparative cell states by lubrication alone, thus revealing the extensive plasticity of these cells and the regenerative function of lubricating the surface. We further show that the generation of a reparative phenotype is due, in part, to disruption of an IL1β autocrine amplification loop promoting chronic inflammation. Thus, our study uncovers the regenerative potential of topical lubrication in dry eye and represents a paradigm shift in our understanding of its therapeutic impact.
角膜润滑是缓解干眼体征和症状最常用的治疗方法，通常被认为主要是姑息性的，没有再生功能。在此，我们对这一观念提出挑战，通过用最简单的润滑形式，即盐溶液，湿润水液缺乏型小鼠模型的干燥角膜，足以挽救严重破坏的富含胶原蛋白的基质结构，基质是角膜最大的部分，对透明度和视力至关重要。在单细胞水平上，我们表明负责维持基质完整性的基质角膜细胞仅通过润滑就从炎症状态转变为独特的修复细胞状态，从而揭示了这些细胞广泛的可塑性以及表面润滑的再生功能。我们进一步表明，修复表型的产生部分归因于促进慢性炎症的IL1β自分泌放大环的破坏。因此，我们的研究揭示了局部润滑在干眼中的再生潜力，并代表了我们对其治疗作用理解的范式转变。
