Identification of systemic biomarkers and potential drug targets for age-related macular degeneration

Area of Science:

• Genetics
• Ophthalmology
• Immunology

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss associated with aging and cellular senescence.
• Cellular senescence involves the accumulation of senescent cells, contributing to age-related diseases.
• Plasma levels of senescence-related proteins (SRPs) may serve as biomarkers for AMD risk.

Purpose of the Study:

• To investigate the association between plasma levels of senescence-related proteins (SRPs) and the risk of developing age-related macular degeneration (AMD).
• To explore the potential causal relationship between specific SRPs and AMD using genetic data.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis was employed.
• Inverse-variance weighted (IVW) method was the primary analytical approach.
• Genome-wide association study (GWAS) data for 110 SRPs and AMD risk from large cohorts (FinnGen and UK Biobank) were utilized.

Main Results:

• Causal associations were found between plasma levels of four SRPs (C3b, CTNNB1, CCL1, and CCL3L1) and increased AMD risk (IVW-P < 0.00045).
• Potential causal links were identified for an additional 10 SRPs.
• No significant heterogeneity or pleiotropy was detected, supporting the robustness of the findings.

Conclusions:

• Elevated plasma levels of C3b, CTNNB1, CCL1, and CCL3L1 are associated with a higher risk of AMD.
• These findings underscore the role of systemic inflammation in AMD pathogenesis.
• The results provide a basis for developing novel preventative and therapeutic strategies for AMD.