Kumar Ajay, Yun Hongmin, Funderburgh Martha L, Du Yiqin
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, 15213, USA; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Prog Retin Eye Res. 2022 Mar;87:101011. doi: 10.1016/j.preteyeres.2021.101011. Epub 2021 Sep 14.
The cornea is the outmost layer of the eye, unique in its transparency and strength. The cornea not only transmits the light essential for vision, also refracts light, giving focus to images. Each of the three layers of the cornea has properties essential for the function of vision. Although the epithelium can often recover from injury quickly by cell division, loss of limbal stem cells can cause severe corneal surface abnormalities leading to corneal blindness. Disruption of the stromal extracellular matrix and loss of cells determining this structure, the keratocytes, leads to corneal opacity. Corneal endothelium is the inner part of the cornea without self-renewal capacity. It is very important to maintain corneal dehydration and transparency. Permanent damage to the corneal stroma or endothelium can be effectively treated by corneal transplantation; however, there are drawbacks to this procedure, including a shortage of donors, the need for continuing treatment to prevent rejection, and limits to the survival of the graft, averaging 10-20 years. There exists a need for new strategies to promote regeneration of the stromal structure and restore vision. This review highlights critical contributions in regenerative medicine with the aim of corneal reconstruction after injury or disease. These approaches include corneal stromal stem cells, corneal limbal stem cells, embryonic stem cells, and other adult stem cells, as well as induced pluripotent stem cells. Stem cell-derived trophic factors in the forms of secretomes or exosomes for corneal regeneration are also discussed. Corneal sensory nerve regeneration promoting corneal transparency is discussed. This article provides description of the up-to-date options for corneal regeneration and presents exciting possible avenues for future studies toward clinical applications for corneal regeneration.
角膜是眼睛的最外层,其透明度和强度独一无二。角膜不仅能传输视觉所需的光线,还能折射光线,使图像聚焦。角膜的三层结构各自具有视觉功能所必需的特性。尽管角膜上皮通常可通过细胞分裂迅速从损伤中恢复,但角膜缘干细胞的缺失会导致严重的角膜表面异常,进而导致角膜失明。角膜基质细胞外基质的破坏以及决定该结构的细胞(角膜细胞)的丧失会导致角膜混浊。角膜内皮是角膜的内层,没有自我更新能力。维持角膜脱水和透明度非常重要。角膜基质或内皮的永久性损伤可通过角膜移植有效治疗;然而,该手术存在一些缺点,包括供体短缺、需要持续治疗以防止排斥反应以及移植物存活期有限,平均为10至20年。因此需要新的策略来促进基质结构的再生并恢复视力。本综述重点介绍了再生医学在角膜损伤或疾病后重建方面的关键贡献。这些方法包括角膜基质干细胞、角膜缘干细胞、胚胎干细胞和其他成体干细胞,以及诱导多能干细胞。还讨论了以分泌组或外泌体形式存在的干细胞衍生营养因子在角膜再生中的作用。探讨了促进角膜透明度的角膜感觉神经再生。本文介绍了角膜再生的最新选择,并为未来角膜再生临床应用的研究提供了令人兴奋的可能途径。