Centre de Recherche du CHU de Québec - Université Laval, Axe Médecine Régénératrice, Hôpital du Saint-Sacrement, Québec, Canada.
Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Québec, Canada.
Invest Ophthalmol Vis Sci. 2023 May 1;64(5):13. doi: 10.1167/iovs.64.5.13.
Fuchs endothelial corneal dystrophy (FECD) is characterized by an accelerated depletion of corneal endothelial cells. There is growing evidence that mitochondrial exhaustion is central in the pathology. Indeed, endothelial cells loss in FECD forces the remaining cells to increase their mitochondrial activity, leading to mitochondrial exhaustion. This generates oxidation, mitochondrial damage, and apoptosis, fueling a vicious cycle of cells' depletion. This depletion ultimately causes corneal edema and irreversible loss of transparency and vision. Concurrently to endothelial cells loss, the formation of extracellular mass called guttae on the Descemet's membrane, is a hallmark of FECD. The pathology origins at the center of the cornea and progress outward, like the appearance of guttae.
Using corneal endothelial explants from patients with late-stage FECD at the time of their corneal transplantation, we correlated mitochondrial markers (mitochondrial mass, potential, and calcium) and the level of oxidative stress and apoptotic cells, with the area taken by guttae. The different markers have been analyzed using fluorescent-specific probes and microscopic analysis.
We observed a positive correlation between the presence of guttae and the level of mitochondrial calcium and apoptotic cells. We found a negative correlation between the presence of guttae and the level of mitochondrial mass, membrane potential, and oxidative stress.
Taken together, these results show that the presence of guttae is correlated with negative outcome in the mitochondrial health, oxidative status, and survival of nearby endothelial cells. This study provides insight on FECD etiology that could lead to treatment targeting mitochondrial stress and guttae.
Fuchs 内皮角膜营养不良（FECD）的特征是角膜内皮细胞的加速耗竭。越来越多的证据表明线粒体衰竭是其病理学的核心。事实上，FECD 中内皮细胞的丧失迫使剩余细胞增加其线粒体活性，导致线粒体衰竭。这会产生氧化、线粒体损伤和细胞凋亡，从而加剧细胞耗竭的恶性循环。这种耗竭最终导致角膜水肿和透明度及视力的不可逆转丧失。与内皮细胞丧失同时发生的是，在 Descemet 膜上形成称为胶滴的细胞外物质，这是 FECD 的一个标志。病理学起源于角膜的中心，并向外发展，就像胶滴的出现一样。
我们使用在角膜移植时患有晚期 FECD 患者的角膜内皮培养物，将线粒体标志物（线粒体质量、电位和钙）以及氧化应激和凋亡细胞的水平与胶滴所占面积进行相关分析。使用荧光特异性探针和显微镜分析对不同的标志物进行了分析。
我们观察到胶滴的存在与线粒体钙和凋亡细胞的水平呈正相关。我们发现胶滴的存在与线粒体质量、膜电位和氧化应激的水平呈负相关。
这些结果表明，胶滴的存在与线粒体健康、氧化状态和附近内皮细胞的存活呈负相关。本研究为 FECD 的病因学提供了深入的了解，这可能导致针对线粒体应激和胶滴的治疗。
