End binding-3 inhibitor activates regenerative program in age-related macular degeneration

Area of Science:

• Ophthalmology
• Cell Biology
• Pharmacology

Background:

• Wet age-related macular degeneration (AMD) is a leading cause of blindness due to abnormal choroidal neovascularization.
• Current treatments involve frequent intravitreal injections of anti-VEGF biologics, necessitating less invasive alternatives.

Purpose of the Study:

• To develop and evaluate EBIN, an allosteric inhibitor of end binding-3 (EB3) protein, as a potential topical treatment for wet AMD.

Main Methods:

• Design of EBIN, an allosteric inhibitor targeting EB3 protein.
• Administration of EBIN via eye drops in mouse and non-human primate models of wet AMD.
• Assessment of EBIN's effects on neovascular leakage, choroidal neovascularization, and epigenetic changes.

Main Results:

• EBIN eye drops effectively prevented neovascular leakage and choroidal neovascularization in preclinical models.
• EBIN reversed stress-induced epigenetic alterations in endothelial cells.
• The treatment activated a regenerative program in metabolically active endothelial cells within CNV lesions.

Conclusions:

• EBIN demonstrates therapeutic potential as a non-invasive, topical treatment for wet AMD.
• Targeting EB3 with EBIN offers a novel strategy to inhibit pathological neovascularization and promote ocular tissue regeneration.