The corneal endothelium is the inner cell monolayer involved in the maintenance of corneal transparence by the generation of homeostatic dehydration. The glycosaminoglycans of the corneal stroma develop a continuous swelling pressure that should be counteracted by the corneal endothelial cells through active transport mechanisms to move the water to the anterior chamber. Protein transporters for sodium (Na⁺), potassium (K⁺), chloride (Cl⁻) and bicarbonate (HCO₃⁻) are involved in this endothelial “pump function”, however despite its physiological importance, the efflux mechanism is not completely understood. There is experimental evidence describing transendothelial diffusion of water in the absence of osmotic gradients. Therefore, it is important to get a deeper understanding of alternative models that drive the fluid transport across the endothelium such as the electrochemical gradients.

Three transcriptomic datasets of the corneal endothelium were used in this study to analyze the expression of genes that encode proteins that participate in the transport and the reestablishment of the membrane potential across the semipermeable endothelium. Subsequently, the expression of the identified channels was validated in vitro both at mRNA and protein levels. The results of this study provide the first evidence of the expression of KCNN2, KCNN3 and KCNT2 genes in the corneal endothelium. Differences among the level of expression of KCNN2, KCNT2 and KCNN4 genes were found in a differentially expressed gene analysis of the dataset. Taken together these results underscore the potential importance of the ionic channels in the pathophysiology of corneal diseases. Moreover, we elucidate novel mechanisms that might be involved in the pivotal dehydrating function of the endothelium and in others physiologic functions of these cells using in silico pathways analysis.

角膜内皮是内细胞单层，通过产生稳态脱水来维持角膜透明。角膜基质的糖胺聚糖产生持续的膨胀压力，角膜内皮细胞应通过主动运输机制将水移动到前房来抵消该压力。钠 (Na ⁺ )、钾 (K ⁺ )、氯化物 (Cl ^- ) 和碳酸氢盐 (HCO ₃ ^- ) 的蛋白质转运蛋白) 参与这种内皮“泵功能”，然而，尽管其生理重要性，外排机制尚未完全了解。有实验证据描述了在没有渗透梯度的情况下水的跨内皮扩散。因此，更深入地了解驱动流体跨内皮传输的替代模型（例如电化学梯度）非常重要。

本研究使用角膜内皮的三个转录组数据集来分析编码蛋白质的基因的表达，这些蛋白质参与运输和跨半透性内皮的膜电位重建。随后，在 mRNA 和蛋白质水平上体外验证了已识别通道的表达。本研究的结果提供了角膜内皮中KCNN2、KCNN3和KCNT2基因表达的第一个证据。KCNN2、KCNT2和KCNN4表达水平的差异在数据集的差异表达基因分析中发现了基因。综上所述，这些结果强调了离子通道在角膜疾病病理生理学中的潜在重要性。此外，我们使用计算机通路分析阐明了可能涉及内皮关键脱水功能和这些细胞的其他生理功能的新机制。