Yin Yiwei, Pu Li, Yang Xi, Zhu Ying, Chen Fang, Wu Chenkun, Lei Hetian, Wu Wenyi
Department of Ophthalmology, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
Commun Biol. 2025 Apr 4;8(1):560. doi: 10.1038/s42003-025-07955-7.
Abnormal blood vessel growth in the eye is a leading cause of vision loss globally, particularly in diseases like diabetic retinopathy where the vitreous plays a crucial but poorly understood role in disease progression. While we know the vitreous can stimulate blood vessel growth, the specific molecular mechanisms remain unclear. Here we show that a protein called G0S2 (G0/G1 switch gene 2) serves as a key regulator of blood vessel growth in response to normal vitreous. Through comprehensive gene analysis, we discovered that G0S2 levels increase significantly when blood vessel cells are exposed to normal vitreous. The importance of G0S2 is highlighted by our finding that uveal melanoma patients with higher G0S2 levels had poorer survival rates. When we removed G0S2 from blood vessel cells, they no longer responded to vitreous stimulation, confirming its critical role. Notably, we identified an existing drug that can target G0S2, potentially offering a new therapeutic approach. This discovery of G0S2's role and its potential therapeutic targeting opens new avenues for treating eye diseases characterized by abnormal blood vessel growth, while also providing a valuable biomarker for predicting disease progression in eye cancer patients.
眼部血管异常生长是全球视力丧失的主要原因，尤其是在糖尿病性视网膜病变等疾病中，玻璃体在疾病进展中起着关键但尚未完全了解的作用。虽然我们知道玻璃体可以刺激血管生长，但具体的分子机制仍不清楚。在这里，我们表明一种名为G0S2（G0/G1转换基因2）的蛋白质是响应正常玻璃体时血管生长的关键调节因子。通过全面的基因分析，我们发现当血管细胞暴露于正常玻璃体时，G0S2水平会显著增加。我们的研究结果突出了G0S2的重要性，即G0S2水平较高的葡萄膜黑色素瘤患者生存率较低。当我们从血管细胞中去除G0S2时，它们不再对玻璃体刺激作出反应，证实了其关键作用。值得注意的是，我们确定了一种可以靶向G0S2的现有药物，这可能提供一种新的治疗方法。G0S2作用的这一发现及其潜在的治疗靶点为治疗以血管异常生长为特征的眼部疾病开辟了新途径，同时也为预测眼癌患者的疾病进展提供了有价值的生物标志物。
