ArticleInvestigative ophthalmology & visual science2022
High Glucose Aggravates Retinal Endothelial Cell Dysfunction by Activating the RhoA/ROCK1/pMLC/Connexin43 Signaling Pathway.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 13 citations in OpenAlex.
- Article
- Pharmacological manipulation of Sema4D by salvianolic acid A mitigates diabetic retinopathy via inhibiting PlexinB1/RhoA/ROCK/pMLC2 signaling cascade involved in endothelial dysfunction.Chinese medicine · 2026Article
- hsa_circ_0068631 facilitates the progression of diabetic retinopathy via regulating miR-140-5p in retinal microvascular endothelial cells.BMC ophthalmology · 2026Article
- Kaempferol Alleviates Glucocorticoid-Induced Osteonecrosis of the Femoral Head by Modulating Macrophage M1/M2 Polarization Through RhoA/ROCK-Mediated Mitophagy Activation.Biomedicines · 2026Article
- ROS-pH Dual-Responsive Polydopamine Nanoparticles for Targeted Fasudil Delivery Ameliorate Multiple Pathologies in Diabetic Retinopathy.International journal of nanomedicine · 2026Article
- Advanced Glycation End Products and Metabolic-Mechanical Coupling in Diabetic Retinopathy.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- Glutaredoxin 2 Protects Lens Epithelial Cells From Ferroptosis by Preventing HNRNPA2B1 S-Glutathionylation in Diabetes-Mediated Cataractogenesis.Investigative ophthalmology & visual science · 2025Article
- What do You Need to Know after Diabetes and before Diabetic Retinopathy?Aging and disease · 2025Review
- Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis.International journal of molecular medicine · 2024Article
- ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.Acta pharmacologica Sinica · 2024Article
- Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26.International journal of molecular sciences · 2024Article
- Circulating small extracellular vesicles mediate vascular hyperpermeability in diabetes.Diabetologia · 2024Article
- Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway.Journal of inflammation research · 2024Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: This research aims to explore the mechanism underlying the relationship between RhoA/ROCK signaling and Connexin43 (Cx43) in retinal endothelial cell dysfunction and to evaluate the protective effect of ROCK inhibitors against retinal endothelial cell dysfunction in diabetic retinopathy (DR) models. Methods: TUNEL staining, hematoxylin and eosin staining, a retinal digestion assay, and Evans blue assay were conducted to explore the effect of fasudil in alleviating retinal dysfunction induced by DR. ELISA, the CCK-8 assay, and flow cytometry were conducted to study inflammation, viability, and apoptosis of mouse retinal microvascular endothelial cells treated with high glucose and ROCK inhibitors. The qRT-PCR and Western blotting were used to evaluate the expression of RhoA, ROCK1, ROCK2, MLC, pMLC, and Cx43. Co-immunoprecipitation was used to verify the interaction between pMLC and Cx43. Immunofluorescence and scrape-loading and dye transfer were used to evaluate the expression and function of Cx43. Results: Marked endothelial cell dysfunction resulting from the activation of RhoA/ROCK1 signaling was found in in vivo and in vitro models of DR. Via interaction with pMLC, which is downstream of RhoA/ROCK1, a significant downregulation of Cx43 was observed in retinal endothelial cells. Treatment with ROCK inhibitors ameliorated retinal endothelial dysfunction in vitro. The ROCK inhibitor, fasudil, significantly alleviated retinal dysfunction as shown by a decrease of retinal acellular capillaries, an improvement of vascular permeability, and a reduction of cell apoptosis in vivo. Conclusions: Our study highlights a novel mechanism that high glucose could activate RhoA/ROCK1/pMLC signaling, which targets the expression and localization of Cx43 and is responsible for cell viability, apoptosis, and inflammation, resulting in retinal endothelial cell injury. ROCK inhibitors markedly ameliorate endothelial cell dysfunction, suggesting their therapeutic potential for diabetic retinopathy.
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