RhoA/ROCK Signaling Is Involved in Pathological Retinal Neovascularization

Fen Tang; Kongqian Huang; Biyan Peng; Wen Deng; Ning Su; Fan Xu; Mingyuan Zhang; Haibin Zhong

doi:10.1159/000533321

RhoA/ROCK Signaling Is Involved in Pathological Retinal Neovascularization

J Vasc Res. 2023;60(4):183-192. doi: 10.1159/000533321. Epub 2023 Sep 1.

Authors

Fen Tang¹, Kongqian Huang¹, Biyan Peng², Wen Deng¹, Ning Su¹, Fan Xu¹, Mingyuan Zhang^{1

2}, Haibin Zhong¹

Affiliations

¹ Department of Ophthalmology, The People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Key Laboratory of Eye Health and Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology and Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, China.
² Laboratory Animal Center, Guangxi Medical University, Nanning, China.

Abstract

Objective: The aim of the study was to evaluate the effect of the RhoA/ROCK inhibitor Fasudil on retinal neovascularization (NV) in vivo and angiogenesis in vitro.

Methods: C57BL/6 was used to establish an OIR model. First, RhoA/ROCK expression was first examined and compared between OIR and healthy controls. Then, we evaluated the effect of Fasudil on pathological retinal NV. Whole-mount retinal staining was performed. The percentage of NV area, the number of neovascular tufts (NVT), and branch points (BP) were quantified. Finally, human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of Fasudil on angiogenesis.

Results: Real-time PCR and Western blotting showed that ROCK expression in retinal tissue was statistically upregulated in OIR. Furthermore, we found that Fasudil attenuated the percentage of NV area, the number of NVT, and BP significantly. In addition, Fasudil could suppress the proliferation and migration of HUVECs induced by VEGF.

Conclusions: RhoA/ROCK might be involved in the pathogenesis of OIR. And its inhibitor Fasudil could suppress retinal NV in vivo and angiogenesis in vitro. Fasudil may be a potential treatment strategy for retinal vascular diseases.

Keywords: Fasudil; Oxygen-induced retinopathy; Retinal neovascularization; RhoA/ROCK.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Human Umbilical Vein Endothelial Cells
Humans
Mice
Mice, Inbred C57BL
Neovascularization, Pathologic / pathology
Retina / metabolism
Retinal Neovascularization* / genetics
Retinal Neovascularization* / metabolism
Retinal Neovascularization* / pathology

Substances

fasudil

Grants and funding

The work was funded by the National Natural Science Foundation of China (No. 82000925), the Natural Science Foundation of Guangxi Zhuang Autonomous Region (No. 2021GXNSFAA220005), Guangxi Clinical Ophthalmic Research Center (No. Guike AD19245193), and Guangxi Science and Technology Base and Talent Special Fund (No. Guike AD19245007).