Feng Wen, Xie Pinxue, Du Yunhui, Duan Yanru, Gao Xinxiao
Department of Ophthalmology, Beijing Anzhen Hospital, Capital Medical University, Beijing, P.R. China.
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P.R. China.
FASEB J. 2025 Mar 31;39(6):e70483. doi: 10.1096/fj.202401528RR.
Retinal neovascularization (RNV) is an important pathological change associated with proliferative diabetic retinopathy (PDR), which is a common cause of vision loss. PDZ and LIM domain protein 1 (PDLIM1) plays an important role in the occurrence and development of nonproliferative diabetic retinopathy (NPDR); however, the role of PDLIM1 in PDR remains unclear. We conducted gain-of-function studies using adenovirus infection and found that PDLIM1 overexpression inhibited the migration, proliferation, and tube formation of vascular endothelial cells. Moreover, PDLIM1 regulated the expression of β-catenin in vascular endothelial cells. Furthermore, in an oxygen-induced retinopathy model, PDLIM1 negatively regulated β-catenin, and the inhibition of PDLIM1 promoted RNV. In contrast, increased PDLIM1 levels significantly inhibited the formation of RNV. In summary, our findings provide evidence that PDLIM1 plays an important role in pathological neovascularization and may serve as a target for the treatment of RNV.
视网膜新生血管形成（RNV）是与增殖性糖尿病视网膜病变（PDR）相关的一种重要病理变化，PDR是视力丧失的常见原因。PDZ和LIM结构域蛋白1（PDLIM1）在非增殖性糖尿病视网膜病变（NPDR）的发生和发展中起重要作用；然而，PDLIM1在PDR中的作用仍不清楚。我们使用腺病毒感染进行了功能获得性研究，发现PDLIM1过表达抑制血管内皮细胞的迁移、增殖和管腔形成。此外，PDLIM1调节血管内皮细胞中β-连环蛋白的表达。此外，在氧诱导的视网膜病变模型中，PDLIM1负向调节β-连环蛋白，抑制PDLIM1可促进RNV。相反，PDLIM1水平升高显著抑制RNV的形成。总之，我们的研究结果提供了证据，表明PDLIM1在病理性新生血管形成中起重要作用，可能作为治疗RNV的靶点。
