Rho-kinase inhibition reduces subretinal fibrosis

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.