Gao Yaping, Zhu Xiaowei, Luo Yulan, Wu Xuefen, Tan Ling, Qiu Haijiang
Department of Ophthalmology, Guangzhou First People's Hospital, Guangzhou, 510180, Guangdong, China.
Zhongshan City People's Hospital, 4 Sunwen Road, Zhongshan, 528403, Guangdong, China.
Eur J Med Res. 2025 Jul 1;30(1):530. doi: 10.1186/s40001-025-02774-2.
Low-level red light (LLRL) irradiation may inhibit myopia occurrence and progression. Understanding how LLRL inhibits fibrosis in human retinal pigment epithelial (hRPE) cells is critical to inhibiting myopia progression and developing novel therapeutic strategies. Here, we explored the effects of LLRL on hRPE cells in a myopia-simulating hypoxic microenvironment and elucidated the mechanisms through which it inhibits scleral remodeling.
We first used the MTT assay to analyze hRPE cell proliferation under hypoxic conditions after LLRL irradiation at varying frequencies over different durations. RNA sequencing was used to screen for key signaling molecules leading to hRPE cell fibrosis. Western blotting, reverse transcription quantitative polymerase chain reaction, and immunofluorescence assay were used to detect the role of ubiquitin binding enzyme E2 C (UBE2C) in hRPE cell fibrosis under LLRL irradiation.
LLRL was noted to regulate the extracellular matrix, inhibiting fibrosis in hypoxic hRPE cells. Moreover, supernatant of LLRL-treated hypoxic hRPE cells inhibited scleral remodeling in human scleral fibroblasts. Mechanistically, LLRL inhibited cell fibrosis by regulating UBE2C activation of the AKT/mTOR pathway.
In a hypoxic environment, LLRL irradiation can prevent fibroblast transformation in hRPE cells, indicating its potential in scleral remodeling inhibition. Our results revealed the molecular mechanism through which red light controls myopia and provide evidence for further basic and clinical research.
低强度红光（LLRL）照射可能抑制近视的发生和发展。了解LLRL如何抑制人视网膜色素上皮（hRPE）细胞中的纤维化对于抑制近视进展和开发新的治疗策略至关重要。在此，我们探讨了LLRL在模拟近视的缺氧微环境中对hRPE细胞的影响，并阐明了其抑制巩膜重塑的机制。
我们首先使用MTT法分析在不同频率和不同持续时间的LLRL照射后，缺氧条件下hRPE细胞的增殖情况。RNA测序用于筛选导致hRPE细胞纤维化的关键信号分子。蛋白质免疫印迹法、逆转录定量聚合酶链反应和免疫荧光分析用于检测泛素结合酶E2 C（UBE2C）在LLRL照射下hRPE细胞纤维化中的作用。
发现LLRL可调节细胞外基质，抑制缺氧hRPE细胞中的纤维化。此外，经LLRL处理的缺氧hRPE细胞的上清液可抑制人巩膜成纤维细胞中的巩膜重塑。机制上，LLRL通过调节UBE2C对AKT/mTOR通路的激活来抑制细胞纤维化。
在缺氧环境中，LLRL照射可防止hRPE细胞中的成纤维细胞转化，表明其在抑制巩膜重塑方面的潜力。我们的研究结果揭示了红光控制近视的分子机制，并为进一步的基础和临床研究提供了证据。
