Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells

Area of Science:

• Ophthalmology
• Immunology
• Genetics

Background:

• The retinal pigment epithelium (RPE) is crucial for retinal health, and its dysfunction is linked to age-related macular degeneration (AMD).
• AMD pathogenesis involves oxidative stress and complement system dysregulation, but local complement sources and regulation within the retina remain unclear.

Purpose of the Study:

• To model and investigate complement component expression in human primary RPE (hpRPE) cells from AMD-risk and non-risk individuals.
• To evaluate the effect of properdin, a complement stabilizer, on hpRPE cell-dependent complement profiles under oxidative stress.

Main Methods:

• Established a model using hpRPE cells to analyze complement component expression at transcript and protein levels.
• Assessed the impact of exogenous properdin on hpRPE cells exposed to oxidative stress, measuring complement-related gene and protein expression.

Main Results:

• hpRPE cells express, store, and secrete complement components, receptors, and regulators.
• AMD-risk genotypes correlated with increased secretion of complement factors D (CFD) and I (CFI).
• Properdin modulated complement gene expression, decreasing inflammatory markers and complement components under oxidative stress, though this effect was time-dependent.

Conclusions:

• hpRPE cells exhibit local, genotype-associated complement production and activation, independent of systemic complement.
• This local complement system in RPE cells presents a potential novel therapeutic target for AMD.