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人类供体角膜中的氧摄取:向心梯度及其在培养中的变化以及与伤口和氨茶碱治疗的相关性

Oxygen uptake in human donor corneas: the centripetal gradient and its changes in culture and correlation with wounds and aminophylline treatment.

作者信息

Sandoval-Castellanos Ana M, Mann Jeevan, Reid Brian, Li Jennifer Y, Mannis Mark J, Zhao Min

机构信息

Department of Ophthalmology & Vision Science, Institute for Regenerative Cures, School of Medicine, University of California, Davis. Davis, California, USA.

Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California, Davis. Davis, California, USA.

出版信息

bioRxiv. 2025 Jun 27:2025.06.26.661845. doi: 10.1101/2025.06.26.661845.

Abstract

Oxygen is a diatomic element abundant in the atmosphere and is essential for homeostatic and metabolic processes within the cornea. The avascular cornea uptakes oxygen from the atmosphere and performs refractory and protective functions that are essential for eyesight. However, the spatial-temporal profile of oxygen uptake (OU) in human corneas remains uncharacterized in literature. Utilizing the micro optrode technique and donor corneas, we demonstrated that the limbus has a significantly higher OU than the cornea center, exhibiting a pattern of centripetal gradient of OU. This pattern is thus conserved in the corneas of mice, rats, non-human primates, and humans, representing a metabolic feature of physiological significance, which may have diagnostic and prognostic value. Being cultured at 37°C and 5% CO, this centripetal pattern became more prominent in the first three days, and less so on day 4. The pattern remained in the corneas with injury, increased OU appears to correlate with wound healing, similar to patterns observed in animal models with a dynamic increase of metabolism in the periphery, followed by the limbus, and subsequent return to baseline. Administration of the drug aminophylline prevented a decrease of OU at day 4. We conclude that the centripetal pattern of OU is conserved across species and in the human cornea. Combined, our results suggest the functional and clinical significance of the mesoscopic metabolism pattern for further study and the use of aminophylline as a therapeutic agent to increase OU and enhance corneal wound healing.

摘要

氧气是大气中含量丰富的双原子元素,对角膜内的稳态和代谢过程至关重要。无血管的角膜从大气中摄取氧气,并执行对视力至关重要的屈光和保护功能。然而,人类角膜中氧气摄取(OU)的时空分布在文献中仍未得到描述。利用微电极技术和供体角膜,我们证明角膜缘的OU明显高于角膜中心,呈现出向心梯度模式。这种模式在小鼠、大鼠、非人类灵长类动物和人类的角膜中都得以保留,代表了一种具有生理意义的代谢特征,可能具有诊断和预后价值。在37°C和5%二氧化碳条件下培养时,这种向心模式在前三天变得更加明显,第四天则不太明显。在受伤的角膜中这种模式依然存在,OU增加似乎与伤口愈合相关,类似于在动物模型中观察到的模式,即周边代谢动态增加,随后是角膜缘,随后恢复到基线水平。给予氨茶碱药物可防止第四天OU的下降。我们得出结论,OU的向心模式在物种间以及人类角膜中都是保守的。综合来看,我们的结果表明介观代谢模式具有功能和临床意义,有待进一步研究,并且氨茶碱可作为一种治疗药物来增加OU并促进角膜伤口愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3006/12262431/4c96372e89fd/nihpp-2025.06.26.661845v1-f0001.jpg

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