Department of Pharmacy, Kindai University, Higashi‑Osaka, Osaka 577‑8502, Japan.
Department of Ophthalmology, Kanazawa Medical University, Kanazawa, Ishikawa 920‑0293, Japan.
Mol Med Rep. 2019 Jun;19(6):5464-5472. doi: 10.3892/mmr.2019.10214. Epub 2019 May 2.
We previously reported that the collapse of ATP production via mitochondrial damage causes ATPase dysfunction, resulting in the onset or progression of lens opacification in cataracts in model rats. In the present study, it was investigated whether the mRNA expression levels of the three subtypes of mitochondrial cytochrome c oxidase (MTCO)1, 2 and 3 and ATP content change with the type and severity of cataracts in human lens. Samples of lens epithelium were collected from Japanese patients during cataract surgery, and the type and severity of the cataracts (grade) were determined according to the WHO classification [cortical (COR), nuclear (NUC), posterior subcapsular (PSC) opacification]. The MTCO1‑3 mRNA expression levels in patients with grade‑1 COR, NUC and PSC opacification were significantly enhanced compared with those of normal patients. The enhanced MTCO1‑3 mRNA levels subsequently decreased in patients with COR, and the MTCO1‑3 mRNA levels and ATP levels in patients with grade‑3 COR were similar to those in normal patients. However, the mRNA expression levels of MTCO3 in patients with grade 3‑NUC opacification and MTCO1‑3 in patients with grade‑3 PSC opacification, along with the ATP content, were significantly lower than in patients without cataracts. In conclusion, it was revealed that ATP production in lens epithelium is enhanced in early‑stage cataracts (grade‑1) in Japanese patients with COR, NUC and PSC opacification. In addition, in severe cataracts (grade‑3), ATP production and content are strongly decreased in Japanese patients with PSC opacification. ATP depletion in human lens epithelium with PSC opacification may promote lens opacification by ATPase dysfunction.
我们之前曾报道过，线粒体损伤导致的 ATP 生成崩溃会引起 ATP 酶功能障碍，从而导致模型大鼠白内障中晶状体混浊的发生或进展。在本研究中，我们研究了人晶状体中三种亚型线粒体细胞色素 c 氧化酶（MTCO）1、2 和 3 的 mRNA 表达水平和 ATP 含量是否会随白内障的类型和严重程度而变化。在白内障手术期间，从日本患者中采集晶状体上皮样本，并根据世界卫生组织（WHO）分类[皮质（COR）、核性（NUC）、后囊下混浊（PSC）]确定白内障的类型和严重程度（等级）。与正常患者相比，1 级 COR、NUC 和 PSC 混浊患者的 MTCO1-3 mRNA 表达水平显著增强。COR 患者的增强 MTCO1-3 mRNA 水平随后降低，而 3 级 COR 患者的 MTCO1-3 mRNA 水平和 ATP 水平与正常患者相似。然而，3 级 NUC 混浊患者的 MTCO3 mRNA 表达水平和 3 级 PSC 混浊患者的 MTCO1-3 mRNA 表达水平以及 ATP 含量均显著低于无白内障患者。总之，结果表明，在日本 COR、NUC 和 PSC 混浊患者的早期白内障（1 级）中，晶状体上皮的 ATP 生成增强。此外，在严重白内障（3 级）中，PSC 混浊的日本患者的 ATP 生成和含量明显降低。PSC 混浊的人晶状体上皮中 ATP 的耗竭可能会通过 ATP 酶功能障碍促进晶状体混浊。
