Proliferative capacity of corneal endothelial cells.

Proliferative capacity of corneal endothelial cells.
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DOI:
10.1016/j.exer.2011.08.014
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发表时间:
2012-02
影响因子:
3.4
通讯作者:
Joyce, Nancy C.
Joyce, Nancy C.
中科院分区:
医学3区
文献类型:
--
作者:
Joyce, Nancy C.

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角膜内皮单层通过其屏障和离子“泵”功能帮助维持角膜透明度。这种透明功能可能会受损,导致内皮细胞密度(ECD)严重丧失、角膜水肿、大泡性角膜病变和视力丧失。虽然穿透性角膜移植术和各种形式的内皮角膜移植术能够恢复角膜透明度,但它们也可能具有需要重新移植或其他治疗的并发症。随着用于角膜移植术的供体角膜在全球范围内日益短缺,更需要找到新的疗法来恢复由于内皮功能障碍而丧失的角膜透明度。因此,研究人员一直在探索替代方法,这些方法可能导致短暂角膜内皮细胞分裂的体内诱导或健康内皮细胞的体外扩增,用于角膜生物工程,作为增加ECD和恢复视力的治疗方法。本文综述了目前有关人类角膜内皮细胞(HCEC)分裂能力的信息,作为开发新疗法的基础。将介绍细胞周期的正调控和负调控信息,作为待讨论研究的背景。探索HCEC增殖能力的研究结果将被提出,并将讨论影响HCEC分裂能力的具体条件。还将介绍已被测试以诱导HCEC瞬时增殖的方法。本文就供体年龄和内皮地形对HCEC相对增殖能力的影响以及核DNA氧化损伤在降低HCEC相对增殖能力中的作用作一综述。最后,将讨论潜在的新研究方向,可以利用和/或提高这些生理上重要的细胞的增殖能力,以开发新的治疗方法来恢复角膜透明度。
The corneal endothelial monolayer helps maintain corneal transparency through its barrier and ionic “pump” functions. This transparency function can become compromised, resulting in a critical loss in endothelial cell density (ECD), corneal edema, bullous keratopathy, and loss of visual acuity. Although penetrating keratoplasty and various forms of endothelial keratoplasty are capable of restoring corneal clarity, they can also have complications requiring re-grafting or other treatments. With the increasing worldwide shortage of donor corneas to be used for keratoplasty, there is a greater need to find new therapies to restore corneal clarity that is lost due to endothelial dysfunction. As a result, researchers have been exploring alternative approaches that could result in the in vivo induction of transient corneal endothelial cell division or the in vitro expansion of healthy endothelial cells for corneal bioengineering as treatments to increase ECD and restore visual acuity. This review presents current information regarding the ability of human corneal endothelial cells (HCEC) to divide as a basis for the development of new therapies. Information will be presented on the positive and negative regulation of the cell cycle as background for the studies to be discussed. Results of studies exploring the proliferative capacity of HCEC will be presented and specific conditions that affect the ability of HCEC to divide will be discussed. Methods that have been tested to induce transient proliferation of HCEC will also be presented. This review will discuss the effect of donor age and endothelial topography on relative proliferative capacity of HCEC, as well as explore the role of nuclear oxidative DNA damage in decreasing the relative proliferative capacity of HCEC. Finally, potential new research directions will be discussed that could take advantage of and/or improve the proliferative capacity of these physiologically important cells in order to develop new treatments to restore corneal clarity.
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