Function-first ligandomics for ocular vascular research and drug target discovery.

Area of Science:

• Ophthalmology
• Molecular Biology
• Drug Discovery

Background:

• Ocular vascular diseases like wet AMD, DME, and PDR involve neovascularization and leakage.
• Current anti-VEGF therapies show limited efficacy and are not approved for all ocular indications.
• Novel therapies targeting VEGF-independent pathways are crucial for unmet clinical needs.

Purpose of the Study:

• To develop novel therapies for ocular vascular diseases by identifying new drug targets.
• To overcome limitations of current anti-VEGF treatments by exploring alternative or combination therapies.
• To efficiently characterize functional activity and therapeutic potential of identified ligands.

Main Methods:

• Developed the first paradigm of ligandomics for global and disease-selective ligand mapping.
• Combined ligandomics with "function-first" and/or "therapy-first" analyses.
• Utilized the unique advantages of the eye and extracellular ligands for analysis.

Main Results:

• Demonstrated a novel approach to systematically and reliably delineate disease-selective angiogenic or vascular leakage factors.
• Showcased the ability to efficiently characterize functional activity, disease selectivity, and therapeutic potential of ligands.
• Highlighted the potential for high efficacy, minimal side effects, and wide therapeutic windows with targeted therapies.

Conclusions:

• Function- or therapy-first ligandomics offer a powerful strategy for ocular vascular research.
• This innovative approach significantly facilitates the development of ligand-guided targeted anti-angiogenic therapies.
• The findings pave the way for more effective treatments for various human eye vascular diseases.