Kempuraj Duraisamy, Mohan Rajiv R
Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65212, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine & Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65212, USA.
Biomedicines. 2022 Feb 1;10(2):339. doi: 10.3390/biomedicines10020339.
Autophagy is a robust cellular mechanism for disposing of harmful molecules or recycling them to cells, which also regulates physiopathological processes in cornea. Dysregulated autophagy causes inefficient clearance of unwanted proteins and cellular debris, mitochondrial disorganization, defective inflammation, organ dysfunctions, cell death, and diseases. The cornea accounts for two-thirds of the refraction of light that occurs in the eyes, but is prone to trauma/injury and infection. The extracellular matrix (ECM) is a noncellular dynamic macromolecular network in corneal tissues comprised of collagens, proteoglycans, elastin, fibronectin, laminins, hyaluronan, and glycoproteins. The ECM undergoes remodeling by matrix-degrading enzymes and maintains corneal transparency. Autophagy plays an important role in the ECM and wound healing maintenance. Delayed/dysregulated autophagy impacts the ECM and wound healing, and can lead to corneal dysfunction. Stromal wound healing involves responses from the corneal epithelium, basement membrane, keratocytes, the ECM, and many cytokines and chemokines, including transforming growth factor beta-1 and platelet-derived growth factor. Mild corneal injuries self-repair, but greater injuries lead to corneal haze/scars/fibrosis and vision loss due to disruptions in the ECM, autophagy, and normal wound healing processes. Presently, the precise role of autophagy and ECM remodeling in corneal wound healing is elusive. This review discusses recent trends in autophagy and ECM modulation in the context of corneal wound healing and homeostasis.
自噬是一种强大的细胞机制，用于清除有害分子或将其循环利用至细胞中，它还调节角膜中的生理病理过程。自噬失调会导致有害蛋白质和细胞碎片清除效率低下、线粒体紊乱、炎症缺陷、器官功能障碍、细胞死亡及疾病。角膜占眼睛光线折射的三分之二，但易受创伤/损伤和感染。细胞外基质（ECM）是角膜组织中的一种无细胞动态大分子网络，由胶原蛋白、蛋白聚糖、弹性蛋白、纤连蛋白、层粘连蛋白、透明质酸和糖蛋白组成。ECM通过基质降解酶进行重塑，并维持角膜透明度。自噬在ECM和伤口愈合维持中起重要作用。自噬延迟/失调会影响ECM和伤口愈合，并可能导致角膜功能障碍。基质伤口愈合涉及角膜上皮、基底膜、角膜细胞、ECM以及许多细胞因子和趋化因子的反应，包括转化生长因子β-1和血小板衍生生长因子。轻度角膜损伤可自我修复，但较严重的损伤会导致角膜混浊/瘢痕/纤维化以及由于ECM、自噬和正常伤口愈合过程中断而导致的视力丧失。目前，自噬和ECM重塑在角膜伤口愈合中的确切作用尚不清楚。本综述讨论了在角膜伤口愈合和稳态背景下自噬和ECM调节的最新趋势。
