Endothelial c-Src Mediates Neovascular Tuft Formation in Oxygen-Induced Retinopathy.

Autor:	Frampton E; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Som P; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Hill B; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Yu A; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Naval-Sanchez M; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Nefzger CM; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Noordstra I; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Gordon E; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia., Schimmel L; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia. Electronic address: l.schimmel@imb.uq.edu.au.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2024 Sep 25. Date of Electronic Publication: 2024 Sep 25.
DOI:	10.1016/j.ajpath.2024.09.003
Abstrakt:	Vascular retinopathy, characterized by abnormal blood vessel growth in the retina, frequently results in vision impairment or loss. Neovascular tufts, a distinctive pathologic feature of this condition, are highly leaky blood vessel structures, exacerbating secondary complications. Despite their clinical significance, the mechanisms underlying tuft development are not fully elucidated, posing challenges for effective management and treatment of vascular retinopathy. This study investigates the role of c-Src in neovascular tuft formation. Although c-Src has been acknowledged as a pivotal regulator in developmental angiogenesis within the retinal vasculature, its specific role in governing pathologic retinal angiogenesis remains to be fully understood. The oxygen-induced retinopathy model was used for neovascular tuft formation in both Cre-mediated vascular-specific c-Src knockout mice and wild-type littermates. High-resolution imaging and analysis of isolated retinas were conducted. c-Src depletion demonstrated a significant reduction in neovascular tufts within the oxygen-induced retinopathy model. This decrease in tuft formation was observed independently of any alterations in cell death, cell proliferation, or cell adhesion, and the absence of c-Src did not impact tuft pericyte coverage and junctional morphology. These findings underline the critical role of c-Src in the pathogenesis of neovascular tufts in vascular retinopathy. Understanding the molecular mechanisms involving c-Src may offer valuable insights for the development of targeted therapies aimed at mitigating vision-threatening complications associated with retinopathy. Competing Interests: Disclosure Statement None declared. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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