Division for Vision Research, Kanazawa Medical University Graduate School of Medical Science, Kahoku, Ishikawa 920‑0293, Japan.
Department of Ophthalmology, Fujita Health University, Toyoake, Aichi 470‑1192, Japan.
Mol Med Rep. 2023 Jan;27(1). doi: 10.3892/mmr.2022.12906. Epub 2022 Dec 9.
Enhancement of density via human lens epithelium (HLE) cell proliferation is the underlying cause of nuclear cataracts. Moreover, our previous epidemiological study demonstrated that the risk of nuclear cataract development is significantly higher under elevated environmental temperatures compared with under lower temperatures. The present study investigated the relationship between temperature and cell proliferation in terms of mitochondrial function, which is a nuclear cataract‑inducing risk factor, using two different HLE cell lines, SRA01/04 and immortalized human lens epithelial cells NY2 (iHLEC‑NY2). Cell proliferation was significantly enhanced under the high‑temperature condition (37.5˚C) in both cell lines. The cell growth levels of SRA01/04 and iHLEC‑NY2 cells cultured at 37.5˚C were 1.20‑ and 1.16‑fold those in the low‑temperature cultures (35.0˚C), respectively. Moreover, the levels of cytochrome c oxidase mRNA (mitochondrial genome, cytochrome c oxidase‑1‑3) and its activity in SRA01/04 and iHLEC‑NY2 cells cultured at 37.5˚C were higher compared with those in cells cultured at 35.0˚C. In addition, adenosine‑5'‑triphosphate (ATP) levels in SRA01/04 and iHLEC‑NY2 cells were also significantly higher at 37.5˚C compared with those at 35.0˚C. By contrast, no significant differences in Na/K‑ATPase or Ca‑ATPase activities were observed between HLE cells cultured at 35.0 and 37.5˚C. These results suggested that expression of the mitochondrial genome was enhanced in high‑temperature culture, resulting in a sufficient ATP content and cell proliferation for lens opacity. Therefore, elevated environmental temperatures may increase the risk of nuclear cataracts caused by HLE cell proliferation via mitochondrial activation.
通过人晶状体上皮 (HLE) 细胞增殖来提高密度是核性白内障的根本原因。此外，我们之前的流行病学研究表明，与低温相比，高温环境下核性白内障发展的风险显著更高。本研究使用两种不同的 HLE 细胞系 SRA01/04 和永生化人晶状体上皮细胞 NY2 (iHLEC-NY2)，从线粒体功能方面研究了温度与细胞增殖之间的关系，线粒体功能是核性白内障的一个诱导风险因素。在两种细胞系中，高温条件（37.5°C）下细胞增殖均显著增强。在 37.5°C 下培养的 SRA01/04 和 iHLEC-NY2 细胞的细胞生长水平分别是在 35.0°C 下培养的细胞的 1.20-和 1.16-倍。此外，在 37.5°C 下培养的 SRA01/04 和 iHLEC-NY2 细胞中线粒体基因组细胞色素 c 氧化酶 mRNA（细胞色素 c 氧化酶 1-3）及其活性水平均高于在 35.0°C 下培养的细胞。此外，在 37.5°C 下培养的 SRA01/04 和 iHLEC-NY2 细胞中的三磷酸腺苷 (ATP) 水平也明显高于在 35.0°C 下培养的细胞。相比之下，在 35.0 和 37.5°C 下培养的 HLE 细胞中的 Na/K-ATP 酶或 Ca-ATP 酶活性没有显著差异。这些结果表明，高温培养中增强了线粒体基因组的表达，从而使细胞增殖产生足够的 ATP 含量和晶状体混浊。因此，通过线粒体激活，高温环境可能会增加 HLE 细胞增殖引起的核性白内障的风险。
