Progress in corneal wound healing.
Progress in corneal wound healing.
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DOI：
10.1016/j.preteyeres.2015.07.002
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发表时间：
2015-11
影响因子：
17.8
通讯作者：
Saghizadeh M
中科院分区：
文献类型：
--
作者：
Ljubimov AV;Saghizadeh M
角膜伤口愈合是一个复杂的过程，涉及细胞死亡、迁移、增殖、分化和细胞外基质重塑。在角膜上皮细胞、基质细胞和内皮细胞的愈合过程中观察到许多相似之处，以及细胞特异性差异。角膜上皮的愈合主要依赖于角膜缘干细胞和基底膜的重塑。在基质愈合过程中，转化生长因子-β系统的激活使角膜基质细胞转化为运动和收缩的肌成纤维细胞。内皮细胞主要通过迁移和扩散愈合，细胞增殖起次要作用。在过去的十年中，许多方面的伤口愈合过程中的不同部分的角膜已阐明，并出现了一些新的治疗方法。角膜缘干细胞的概念得到了严格的实验证实，新的标记物被发现，新的治疗选择包括在实验系统中测试的基因和microRNA治疗。角膜缘干细胞富集培养物移植用于干细胞缺乏和角膜损伤的有效再上皮化已成为临床环境中的现实。基质愈合过程中的介质和事件过程已被详细说明，并设计了新的治疗方案，包括基因（核心蛋白聚糖）和干细胞治疗过度愈合。这是一个非常重要的进步，因为各种屈光手术的普及需要基质伤口愈合。替换患病内皮的成功手术方法已经在临床上进行了测试，并且已经提出了加速内皮愈合和抑制内皮-间充质转化的新方法，包括Rho激酶（ROCK）抑制剂滴眼液和激活TGF-β抑制剂SMAD 7的基因治疗。有前途的新技术与角膜伤口愈合的操作，包括microRNA，诱导多能干细胞产生角膜上皮，和角膜药物输送的纳米载体进行了讨论。伤口愈合理解和治疗中的问题也受到关注，例如缺乏特异性上皮干细胞标记物，干细胞的可靠鉴定，有效预防haze和基质瘢痕形成，缺乏关于角膜细胞和内皮细胞中伤口调节microRNA的数据，以及实际上缺乏用于药物和基因递送以选择角膜细胞的靶向系统。
Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.