Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC...

Area of Science:

• Ophthalmology
• Immunology
• Vascular Biology

Background:

• Diabetic retinopathy (DR) progression is linked to retinal membrane attack complex (MAC) deposition.
• Circulating IgG-laden extracellular vesicles (EVs) increase retinal vascular permeability in DR via complement activation.

Purpose of the Study:

• To elucidate the mechanism of EV-induced complement activation leading to retinal vascular cytolytic damage in DR.
• To investigate the role of IgG-laden EVs in MAC deposition and endothelial cell damage in DR.

Main Methods:

• Studied IgG-laden EVs in rat plasma and their effect on the classical complement pathway.
• Utilized in vitro Streptozotocin (STZ)-induced rat diabetic plasma with human retinal endothelial cells (HRECs).
• Assessed MAC deposition and cytolytic damage in HRECs.
• Evaluated the impact of EV removal from plasma on MAC deposition and HREC damage.

Main Results:

• IgG-laden EVs in rat plasma activate the classical complement pathway.
• STZ-induced diabetic rat plasma induced MAC deposition and cytolytic damage in HRECs.
• Removal of plasma EVs significantly reduced MAC deposition and abrogated cytolytic damage in HRECs.

Conclusions:

• Complement activation by IgG-laden EVs in plasma contributes to MAC deposition.
• This process leads to endothelial cell damage, potentially driving diabetic retinopathy progression.
• Targeting EVs or complement activation may offer therapeutic strategies for DR.