Ishibashi_2025_J.Pharmacol.Sci_157_57

Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, and inflammation and oxidative stress contribute to DR development. However, no effective treatments are currently approved for DR. Therefore, this study aimed to investigate the effects of SMTP-44D-a Stachybotrys microspora-derived compound with anti-inflammatory and antioxidant properties-on DR in in vivo and in vitro models. Diabetes was induced in rats using 60 mg/kg streptozocin, followed by treatment with SMTP-44D every second day. Retinal function was assessed using electroretinography every 2 months for 8 months. SMTP-44D prevented diabetes-induced b-wave amplitude reductions in electroretinogram and decreased retinal ganglion cell apoptosis. SMTP-44D also reduced the accumulation of advanced glycation end-products (AGEs), AGE receptors, and 8-hydroxydeoxyguanosine in the retina. Furthermore, when rat retinal Mller cells were cultured in DMEM medium containing 35 mM glucose (high glucose, HG) and treated with SMTP-44D for 24 h, SMTP-44D mitigated cell death, reactive oxygen species production, and inflammatory cytokine levels in the cells. These findings suggest that SMTP-44D exhibits significant antioxidant and anti-inflammatory effects, highlighting its potential as a therapeutic candidate for DR.