Systemic human CR2-targeted complement alternative pathway inhibitor ameliorates mouse laser-induced choroidal...

Area of Science:

• Ophthalmology
• Immunology
• Genetics

Background:

• Age-related macular degeneration (AMD) is hypothesized to result from chronic local complement activation.
• The alternative complement pathway is a proposed therapeutic target due to its role in complement amplification.
• A novel factor H (fH)-based complement inhibitor, CR2-fH (TT30), was developed to target C3 activation sites.

Purpose of the Study:

• To evaluate the efficacy of the human therapeutic TT30 in a mouse model of AMD.
• To determine if TT30 can reduce choroidal neovascularization (CNV) and associated pathological changes.

Main Methods:

• CNV was induced in mice using argon laser photocoagulation.
• Mice received intravenous injections of TT30 or vehicle control every other day.
• CNV area, photoreceptor function, complement gene expression, VEGF levels, and TT30 bioavailability were assessed.

Main Results:

• Intravenous TT30 administration significantly reduced CNV development and angiogenesis.
• TT30 ameliorated AMD-related biomarkers, including diminished retinal function and reduced VEGF production.
• The therapeutic agent TT30 localized to CNV lesion sites in the retinal pigmented epithelium-choroid.

Conclusions:

• Systemic administration of TT30 effectively reduced CNV pathology in a preclinical model.
• These findings suggest TT30 as a potential novel therapeutic strategy for systemic AMD treatment.