Corneal endothelium is the single layer of cells forming a boundary between the corneal stroma and anterior chamber. The barrier and "pump" functions of the endothelium are responsible for maintaining corneal transparency by regulating stromal hydration. Morphological studies have demonstrated an age-related decrease in endothelial cell density and indicate that the endothelium in vivo either does not proliferate at all or proliferates at a rate that does not keep pace with the rate of cell loss. Lack of a robust proliferative response to cell loss makes the endothelium, at best, a fragile tissue. As a result of excessive cell loss due to accidental or surgical trauma, dystrophy, or disease, the endothelium may no longer effectively act as a barrier to fluid flow from the aqueous humor to the stroma. This loss of function can cause corneal edema, decreased corneal clarity, and loss of visual acuity, thus requiring corneal transplantation to restore normal vision. Studies from this and other laboratories indicate that corneal endothelium in vivo DOES possess proliferative capacity, but is arrested in G1-phase of the cell cycle. It appears that several intrinsic and extrinsic factors together contribute to maintain the endothelium in a non-replicative state. Ex vivo studies comparing cell cycle kinetics in wounded endothelium of young (< 30 years old) and older donors ( > 50 years old) provide evidence that cells from older donors can enter and complete the cell cycle; however, the length of G1-phase appears to be longer and the cells require stronger mitogenic stimulation than cells from younger donors. In vivo conditions per se also contribute to maintenance of a non-replicative monolayer. Endothelial cells are apparently unable to respond to autocrine or paracrine stimulation even though they express mRNA and protein for a number of growth factors and their receptors. Exogenous transforming growth factor-beta (TGF-beta) and TGF-beta in aqueous humor suppress S-phase entry in cultured endothelial cells, suggesting that this cytokine could inhibit proliferation in vivo. In addition, cell-cell contact appears to inhibit endothelial cell proliferation during corneal development and to help maintain the mature endothelial monolayer in a non-proliferative state, in part, via the activity of p27kip1, a known G1-phase inhibitor. The fact that human corneal endothelium retains proliferative capacity has led to recent efforts to induce division and increase the density of these important cells. For example, recent studies have demonstrated that adult human corneal endothelial cells can be induced to grow in culture and then transplanted to recipient corneas ex vivo. The laboratory work that has been conducted up to now opens an exciting new door to the future. The time is right to apply the knowledge that has been gained regarding corneal endothelial cell proliferative capacity and regulation of its cell cycle to develop new therapies to treat patients at risk for vision loss due to low endothelial cells counts.

中文翻译：

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角膜内皮细胞的增殖能力。

角膜内皮是在角膜基质和前房之间形成边界的单层细胞。内皮的屏障和“泵”功能负责通过调节基质水合来维持角膜透明性。形态学研究表明，内皮细胞密度与年龄相关，并且表明内皮细胞在体内根本不增殖或以与细胞丢失速率不同步的速率增殖。缺乏对细胞丢失的强有力的增殖反应使得内皮充其量是脆弱的组织。由于意外或外科创伤，营养不良或疾病引起的细胞过度流失的结果，内皮细胞可能不再有效地阻碍液体从房水流向基质。这种功能丧失会导致角膜水肿，角膜清晰度降低和视力丧失，因此需要进行角膜移植以恢复正常视力。来自该实验室和其他实验室的研究表明，体内DOES具有角膜内皮细胞的增殖能力，但被阻滞在细胞周期的G1期。看来，几种内在和外在因素共同有助于将内皮维持在非复制状态。体外研究比较了年轻的（<30岁）和年长的供体（> 50岁）的受伤内皮细胞的细胞周期动力学，提供了证据表明来自较老的供体的细胞可以进入并完成细胞周期。然而，G1期的长度似乎更长，并且细胞比来自年轻供体的细胞需要更强的促有丝分裂刺激。体内条件本身也有助于维持非复制性单层。内皮细胞显然不响应自分泌或旁分泌刺激，即使它们表达多种生长因子及其受体的mRNA和蛋白质。房水中的外源转化生长因子-β（TGF-β）和TGF-β抑制了培养的内皮细胞中的S期进入，表明该细胞因子可以抑制体内增殖。此外，细胞间的接触似乎可以部分抑制角膜发育过程中内皮细胞的增殖，并通过部分已知的G1期抑制剂p27kip1的活性帮助将成熟的内皮单层保持在非增殖状态。人角膜内皮细胞保持增殖能力这一事实导致最近努力诱导这些重要细胞的分裂并增加其密度。例如，最近的研究表明，可以诱导成人角膜内皮细胞在培养物中生长，然后离体移植到受体角膜中。迄今为止进行的实验室工作为未来打开了令人振奋的新门。现在是时候应用有关角膜内皮细胞增殖能力和调节其细胞周期的知识来开发新的疗法，以治疗由于内皮细胞数量低而有视力丧失风险的患者。最近的研究表明，成人角膜内皮细胞可以被诱导在培养物中生长，然后离体移植到受体角膜中。迄今为止进行的实验室工作为未来打开了令人振奋的新门。现在是时候应用有关角膜内皮细胞增殖能力和调节其细胞周期的知识来开发新的疗法，以治疗由于内皮细胞数量低而有视力丧失风险的患者。最近的研究表明，成人角膜内皮细胞可以被诱导在培养物中生长，然后离体移植到受体角膜中。迄今为止进行的实验室工作为未来打开了令人振奋的新门。现在是时候应用有关角膜内皮细胞增殖能力和调节其细胞周期的知识来开发新的疗法，以治疗由于内皮细胞数量低而有视力丧失风险的患者。