Yuebing Li, Tural Yarahmadov, Laura Jahnke, Tess Brodie, Sophia C Morandi, Deborah Stroka, Ali Hafezi-Moghadam, Martin S Zinkernagel, Volker Enzmann, Souska Zandi
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Subretinal fibrosis, a consequence of choroidal neovascularization (CNV) in age-related macular degeneration (AMD), leads to irreversible vision loss due to excessive accumulation of extracellular matrix (ECM) proteins and fibrotic scarring. Anti-VEGF therapy can reverse neovascularization, but its effect on fibrosis is relatively limited. To reduce the visual impact of the fibrosis that remains after CNV. Our study investigated the use of ROCK inhibitors, fasudil and belumosudil, to treat subretinal fibrosis after CNV. The results confirmed that levels of key fibrotic markers (TGF-β1, fibronectin, vimentin, α-SMA and pMYPT1) were lower after treatment. IMC provided detailed spatial mapping of protein expression, revealing significant changes in structure and cellular composition before and after the treatment. We found that fasudil and belumosudil are effective in attenuating subretinal fibrosis by modulating the ROCK-signaling pathway, reducing ECM remodeling and attenuating the expression of markers associated with fibrosis. We hope to provide a basis for maximizing clinical benefit, focusing on optimizing dose and timing of treatment, exploring combination therapies for future anti-subretinal fibrosis research.
期刊介绍：
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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