Department of Ophthalmology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; School of Medicine, University of South Carolina, Columbia, SC, USA; Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA.
Department of Ophthalmology, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Institute for Neuro-Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA.
Exp Eye Res. 2023 Mar;228:109390. doi: 10.1016/j.exer.2023.109390. Epub 2023 Jan 22.
Aquaporins (AQPs) are transmembrane water channel proteins that regulate the movement of water through the plasma membrane in various tissues including cornea. The cornea is avascular and has specialized microcirculatory mechanisms for homeostasis. AQPs regulate corneal hydration and transparency for normal vision. Currently, there are 13 known isoforms of AQPs that can be subclassified as orthodox AQPs, aquaglyceroporins (AQGPs), or supraquaporins (SAQPs)/unorthodox AQPs. AQPs are implicated in keratocyte function, inflammation, edema, angiogenesis, microvessel proliferation, and the wound-healing process in the cornea. AQPs play an important role in wound healing by facilitating the movement of corneal stromal keratocytes by squeezing through tight stromal matrix and narrow extracellular spaces to the wound site. Deficiency of AQPs can cause reduced concentration of hepatocyte growth factor (HGF) leading to reduced epithelial proliferation, reduced/impaired keratocyte migration, reduced number of keratocytes in the injury site, delayed and abnormal wound healing process. Dysregulated AQPs cause dysfunction in osmolar homeostasis as well as wound healing mechanisms. The cornea is a transparent avascular tissue that constitutes the anterior aspect of the outer covering of the eye and aids in two-thirds of visual light refraction. Being the outermost layer of the eye, the cornea is prone to injury. Of the 13 AQP isoforms, AQP1 is expressed in the stromal keratocytes and endothelial cells, and AQP3 and AQP5 are expressed in epithelial cells in the human cornea. AQPs can facilitate wound healing through aid in cellular migration, proliferation, migration, extracellular matrix (ECM) remodeling and autophagy mechanism. Corneal wound healing post-chemical injury requires an integrative and coordinated activity of the epithelium, stromal keratocytes, endothelium, ECM, and a battery of cytokines and growth factors to restore corneal transparency. If the chemical injury is mild, the cornea will heal with normal clarity, but severe injuries can lead to partial and/or permanent loss of corneal functions. Currently, the role of AQPs in corneal wound healing is poorly understood in the context of chemical injury. This review discusses the current literature and the role of AQPs in corneal homeostasis, wound repair, and potential therapeutic target for acute and chronic corneal injuries.
水通道蛋白（AQP）是跨膜水通道蛋白，可调节各种组织（包括角膜）的质膜中水的运动。角膜无血管，具有专门的微循环机制以维持内环境稳定。AQP 调节角膜水合作用和透明度以维持正常视力。目前，已知有 13 种 AQP 同工型，可分为经典 AQP、水甘油通道蛋白（AQGP）或超水通道蛋白（SAQP）/非经典 AQP。AQP 参与角膜成纤维细胞功能、炎症、水肿、血管生成、微血管增殖和角膜愈合过程。AQP 通过挤压穿过紧密的基质基质和狭窄的细胞外空间到达伤口部位，促进角膜基质成纤维细胞的运动，在伤口愈合中发挥重要作用。AQP 缺乏会导致肝细胞生长因子（HGF）浓度降低，从而导致上皮细胞增殖减少、角膜成纤维细胞迁移减少/受损、损伤部位的角膜成纤维细胞数量减少、愈合过程延迟和异常。AQP 失调会导致渗透稳态和伤口愈合机制功能障碍。角膜是一种透明的无血管组织，构成眼睛外部覆盖物的前表面，并有助于三分之二的可见光折射。作为眼睛的最外层，角膜容易受伤。在 13 种 AQP 同工型中，AQP1 表达于基质成纤维细胞和内皮细胞，AQP3 和 AQP5 表达于人角膜上皮细胞。AQP 可通过促进细胞迁移、增殖、迁移、细胞外基质（ECM）重塑和自噬机制促进伤口愈合。化学损伤后的角膜伤口愈合需要上皮、基质成纤维细胞、内皮细胞、ECM 和一系列细胞因子和生长因子的整合和协调活动，以恢复角膜透明度。如果化学损伤较轻，角膜将恢复正常清晰度，但严重损伤可导致部分和/或永久性丧失角膜功能。目前，AQP 在化学性损伤角膜愈合中的作用尚不清楚。本文综述了目前关于 AQP 在角膜内环境稳定、伤口修复以及急性和慢性角膜损伤潜在治疗靶点中的作用的文献。
