Ophthalmology Research Laboratory, Department of Ophthalmology, Kaplan Medical Center, Israel.
Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Invest Ophthalmol Vis Sci. 2024 Jun 3;65(6):14. doi: 10.1167/iovs.65.6.14.
The integrity of the corneal epithelium is essential in maintaining normal corneal function. Conditions disrupting the corneal epithelial layer range from chemical burns to dry eye disease and may result in impairment of both corneal transparency and sensation. Identifying factors that regulate corneal wound healing is key for the development of new treatment strategies. Here, we investigated a direct role of mitochondria in corneal wound healing via mitochondria transplantation.
Human corneal epithelial cells (hCECs) were isolated from human corneas and incubated with mitochondria which were isolated from human ARPE-19 cells. We determined the effect of mitochondria transplantation on wound healing and proliferation of hCECs. In vivo, we used a mouse model of corneal chemical injury. Mitochondria were isolated from mouse livers and topically applied to the ocular surface following injury. We evaluated the time of wound repair, corneal re-epithelization, and stromal abnormalities.
Mitochondria transplantation induced the proliferation and wound healing of primary hCECs. Further, mitochondria transplantation promoted wound healing in vivo. Specifically, mice receiving mitochondria recovered twice as fast as control mice following corneal injury, presenting both enhanced and improved repair. Corneas treated with mitochondria demonstrated the re-epithelization of the wound area to a multi-layer appearance, compared to thinning and complete loss of the epithelium in control mice. Mitochondria transplantation also prevented the thickening and disorganization of the corneal stromal lamella, restoring normal corneal dehydration.
Mitochondria promote corneal re-epithelization and wound healing. Augmentation of mitochondria levels via mitochondria transplantation may serve as an effective treatment for inducing the rapid repair of corneal epithelial defects.
角膜上皮的完整性对于维持正常的角膜功能至关重要。从化学灼伤到干燥性眼病等各种破坏角膜上皮层的情况都可能导致角膜透明度和感觉受损。确定调节角膜伤口愈合的因素是开发新治疗策略的关键。在这里，我们通过线粒体移植研究了线粒体在角膜伤口愈合中的直接作用。
从人眼角膜中分离出人角膜上皮细胞（hCEC），并与从人 ARPE-19 细胞中分离的线粒体孵育。我们确定了线粒体移植对 hCEC 伤口愈合和增殖的影响。在体内，我们使用了角膜化学损伤的小鼠模型。从鼠肝中分离出线粒体，并在损伤后局部应用于眼表面。我们评估了伤口修复、角膜再上皮化和基质异常的时间。
线粒体移植诱导原代 hCEC 的增殖和伤口愈合。此外，线粒体移植促进了体内伤口愈合。具体来说，与对照组小鼠相比，接受线粒体的小鼠在角膜损伤后恢复速度快了两倍，表现出更快、更好的修复。与对照组小鼠相比，用线粒体处理的角膜显示出伤口区域的再上皮化，呈现多层外观，而对照组小鼠的角膜上皮变薄并完全丧失。线粒体移植还防止了角膜基质板层的增厚和结构紊乱，恢复了正常的角膜脱水。
线粒体促进角膜再上皮化和伤口愈合。通过线粒体移植增加线粒体水平可能成为诱导角膜上皮缺陷快速修复的有效治疗方法。
