Current eye research · 2026
The Role of Plasminogen Activator Inhibitor-1 in Uveitis: Findings from Clinical and Experimental Studies.
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Suzuki Kayo, Iwata Daiju, Namba Kenichi, Hase Keitaro, Hiraoka Miki, Murata Miyuki, Kitaichi Nobuyoshi, Ohno Shigeaki, Ishida Susumu
Аннотация
PURPOSE: Plasminogen activator inhibitor (PAI) -1 is a key regulator of endogenous fibrinolysis and is widely acknowledged as a its primary inhibitor. Beyond this function, PAI-1 also plays a role in macrophage migration during inflammatory conditions. This study aims to investigate the contribution of PAI-1 to the progression of uveitis.
METHODS: We quantified PAI-1 protein levels in vitreous samples collected from uveitis patients utilizing a magnetic bead-based multiplex immunoassay. To clarify the changes in PAI-1 expression in uveitis, experimental autoimmune uveoretinitis (EAU) was induced in mice through immunization with bovine retinal antigens. The mRNA levels of PAI-1 in the retinochoroidal tissues of EAU mice and control mice, which were immunized without retinal antigen, were examined using quantitative real-time RT-PCR. The severity of EAU treated with the PAI-1 inhibitor; IMD4482, was clinically assessed over time. Furthermore, THP-1 macrophages were cultured with PAI-1 and each concentration of IMD4482 (0 μM, 0.1 μM, 1 μM, 10 μM and 100 μM) for 24 h. The number of migrated cells was quantified using a transwell assay.
RESULTS: Vitreous PAI-1 protein levels were markedly eleveted in uveitis patients compared to controls (p < 0.01). In EAU mice, retinochoroidal PAI-1 mRNA expression was significantly higher than in control mice (n = 6, p = 0.03). Treatment with IMD4482 significantly reduced the clinical severity of EAU (n = 18-20, p < 0.01) and the migration of THP-1 macrophages was significantly inhibited by IMD4482 (100 μM; p < 0.01).
CONCLUSION: Our findings indicate that the level of PAI-1 is locally high in the eye of uveitis patients as well as in experimental uveitis models. Suppression of EAU through PAI-1 inhibition highlights its potential as a therapeutic target for uveitis.
METHODS: We quantified PAI-1 protein levels in vitreous samples collected from uveitis patients utilizing a magnetic bead-based multiplex immunoassay. To clarify the changes in PAI-1 expression in uveitis, experimental autoimmune uveoretinitis (EAU) was induced in mice through immunization with bovine retinal antigens. The mRNA levels of PAI-1 in the retinochoroidal tissues of EAU mice and control mice, which were immunized without retinal antigen, were examined using quantitative real-time RT-PCR. The severity of EAU treated with the PAI-1 inhibitor; IMD4482, was clinically assessed over time. Furthermore, THP-1 macrophages were cultured with PAI-1 and each concentration of IMD4482 (0 μM, 0.1 μM, 1 μM, 10 μM and 100 μM) for 24 h. The number of migrated cells was quantified using a transwell assay.
RESULTS: Vitreous PAI-1 protein levels were markedly eleveted in uveitis patients compared to controls (p < 0.01). In EAU mice, retinochoroidal PAI-1 mRNA expression was significantly higher than in control mice (n = 6, p = 0.03). Treatment with IMD4482 significantly reduced the clinical severity of EAU (n = 18-20, p < 0.01) and the migration of THP-1 macrophages was significantly inhibited by IMD4482 (100 μM; p < 0.01).
CONCLUSION: Our findings indicate that the level of PAI-1 is locally high in the eye of uveitis patients as well as in experimental uveitis models. Suppression of EAU through PAI-1 inhibition highlights its potential as a therapeutic target for uveitis.