Center for Integrative Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto, Japan.
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Nat Biomed Eng. 2019 Dec;3(12):953-960. doi: 10.1038/s41551-019-0429-9. Epub 2019 Jul 22.
Dysfunction of the corneal endothelium reduces the transparency of the cornea and can cause blindness. Because corneal endothelial cells have an extremely limited proliferative ability in vivo, treatment for corneal endothelial dysfunction involves the transplantation of donor corneal tissue. Corneal endothelium can also be restored via intraocular injection of endothelial cells in suspension after their expansion in vitro. Yet, because quality assessment during the expansion of the cells is a destructive process, a substantial number of the cultured cells are lost. Here, we show that the 'spring constant' of the effective interaction potential between endothelial cells in a confluent monolayer serves as a biomarker of the quality of corneal endothelial cells in vitro and of the long-term prognosis of corneal restoration in patients treated with culture-expanded endothelial cells or with transplanted corneas. The biomarker can be measured from phase contrast imaging in vitro and from specular microscopy in vivo, and may enable a shift from passive monitoring to pre-emptive intervention in patients with severe corneal disorders.
角膜内皮功能障碍会降低角膜的透明度，并可能导致失明。由于角膜内皮细胞在体内的增殖能力极其有限，因此治疗角膜内皮功能障碍涉及供体角膜组织的移植。角膜内皮也可以通过在体外扩增后将悬浮的内皮细胞眼内注射来恢复。然而，由于在细胞扩增过程中的质量评估是一个破坏性的过程，因此大量培养的细胞丢失。在这里，我们表明，在致密单层中内皮细胞之间的有效相互作用势的“弹性常数”可作为体外角膜内皮细胞质量的生物标志物，以及接受培养扩增的内皮细胞或移植角膜治疗的患者的角膜恢复的长期预后的生物标志物。该生物标志物可以通过体外相差成像和体内共焦显微镜测量，并且可能使严重角膜疾病患者从被动监测转变为主动干预。
