Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE...

Area of Science:

• Ophthalmology
• Immunology
• Genetics

Background:

• Polymorphisms in complement genes are associated with age-related macular degeneration (AMD) risk.
• Risk-associated polymorphisms lead to impaired control of the alternative complement pathway.

Purpose of the Study:

• Investigate terminal complement complex (TCC) levels in wet AMD patients.
• Determine the impact of AMD patient plasma complement activation on retinal pigment epithelium (RPE) cells.

Main Methods:

• Plasma collection from 87 wet AMD patients and 86 controls.
• Genotyping for risk alleles (CFH 402HH, ARMS2 rs3750846) and TCC level determination.
• In vitro analysis of RPE function, including Ca2+ imaging and gene/cytokine expression.

Main Results:

• AMD patients had fivefold higher plasma TCC levels than controls, irrespective of genetic risk alleles.
• Patient plasma induced distinct Ca2+ signaling in RPE cells, correlating with TCC levels.
• Exposure to AMD patient plasma sensitized RPE cells, increasing pro-inflammatory cytokine secretion and protective gene expression.

Conclusions:

• Elevated plasma TCC levels are a significant factor in AMD pathology.
• AMD patient plasma induces a pro-inflammatory RPE phenotype and protective responses against TCC.
• The observed effects were independent of common AMD genetic risk factors.