LCB54-0009: A Potent Inhibitor of Ocular Angiogenesis and Lymphangiogenesis in Experimental Eye Diseases

The research explores the relationship between abnormal blood and lymphatic vessel growth and human diseases, particularly eye conditions. It suggests that substances which can inhibit these processes might offer a promising treatment for such diseases. The study utilized both laboratory and animal models to evaluate angiogenesis and lymphangiogenesis under conditions of VEGF stimulation or hypoxia in endothelial and retinal cells.

The key finding was that an imidazole-based compound, referred to as LCB54-0009, effectively prevented the formation of blood vessels in VEGF-stimulated HUVECs without causing cell damage. When injected into the eyes of mice and rats, it reduced abnormal blood vessel growth and vascular permeability in conditions mimicking retinopathy. Additionally, when applied to the cornea, it mitigated inflammation and related blood and lymph vessel growth in both mice and rats.

The compound's therapeutic effects are believed to be linked to its impact on HIF-1α protein stability and the redox sensitivity of HIF-1α/NF-κB, along with its antioxidant properties. It also suppressed the expression of angiopoietin-2 under hypoxic conditions and hindered VEGF-induced VEGFR-2 activation and related signaling pathways. This resulted in a decrease in pro-angiogenic and pro-inflammatory factors and an increase in anti-angiogenic factors.

In conclusion, the study posits that LCB54-0009 could be a viable candidate for therapeutic intervention against pathological blood and lymphatic vessel growth, mediated through HIF-1α-angiopoietin-2 expression and VEGFR-2 activation.