Niu Rui, Nie Ze-Tong, Liu Lin, Chang Yu-Wen, Shen Jian-Qun, Chen Qiong, Dong Li-Jie, Hu Bo-Jie
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Hetian District People's Hospital, Xinjiang, China.
Aging (Albany NY). 2021 Mar 10;13(6):8643-8664. doi: 10.18632/aging.202678.
The degree of retinal fibrosis increased in proliferative diabetic retinopathy (PDR) patients after administration of anti-Vascular endothelial growth factor (VEGF) injections. Previous studies showed that the balance between connective tissue growth factor (CTGF) and VEGF plays an important role. Therefore, in a high-glucose state, an anti-VEGF and CTGFshRNA dual-target model was used to simulate clinical dual-target treatment in PDR patients, and RNA sequencing (RNA-Seq) technology was used for whole transcriptome sequencing. A hypoxia model was constructed to verify the sequencing results at the cellular level, and the vitreous humor and proliferative membranes were collected from patients for verification. All sequencing results included Follistatin-like protein 1 () and extracellular matrix (ECM) receptor pathway, indicated that anti-VEGF therapy may upregulate FSTL1 expression, while dual-target treatment downregulated FSTL1. Thus, we further studied the function of FSTL1 on the expression of VEGF and ECM factors by both overexpressing and silencing . In conclusion, our results suggested that FSTL1 may be involved in the pathogenesis of PDR and is related to fibrosis caused by the anti-VEGF treatment, thus providing a potential target for gene therapy in PDR.
在增殖性糖尿病视网膜病变（PDR）患者中，抗血管内皮生长因子（VEGF）注射治疗后视网膜纤维化程度增加。先前的研究表明，结缔组织生长因子（CTGF）和VEGF之间的平衡起着重要作用。因此，在高糖状态下，使用抗VEGF和CTGFshRNA双靶点模型模拟PDR患者的临床双靶点治疗，并采用RNA测序（RNA-Seq）技术进行全转录组测序。构建缺氧模型在细胞水平验证测序结果，并收集患者的玻璃体液和增殖膜进行验证。所有测序结果包括卵泡抑素样蛋白1（）和细胞外基质（ECM）受体途径，表明抗VEGF治疗可能上调FSTL1表达，而双靶点治疗下调FSTL1。因此，我们通过过表达和沉默进一步研究了FSTL1对VEGF和ECM因子表达的作用。总之，我们的结果表明，FSTL1可能参与PDR的发病机制，并与抗VEGF治疗引起的纤维化有关，从而为PDR的基因治疗提供了一个潜在靶点。
