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

• Published in: International journal of molecular sciences Vol. 21; no. 5; p. 1693
• Main Authors: Huang, Chao, Fisher, Kiera P, Hammer, Sandra S, Busik, Julia V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2020; MDPI
• Subjects: Complement; Complement activation; complement system; Cytotoxicity; Deposition; Diabetes; Diabetes mellitus; Diabetic retinopathy; Endothelial cells; Endothelium; Extracellular vesicles; human retinal endothelial cells (hrecs); Immunoglobulin G; Immunoglobulins; Membrane attack complex; membrane attack complex (mac); Permeability; Proteins; Retina; retinal vascular damage; Retinopathy; Streptozocin; Veins & arteries; Vesicles; extracellular vesicles; human retinal endothelial cells (HRECs); diabetic retinopathy; retinal vascular damage; membrane attack complex (MAC); complement system
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21051693

Several studies have suggested that there is a link between membrane attack complex (MAC) deposition in the retina and the progression of diabetic retinopathy (DR). Our recent investigation demonstrated that circulating IgG-laden extracellular vesicles contribute to an increase in retinal vascular permeability in DR through activation of the complement system. However, the mechanism through which extracellular vesicle-induced complement activation contributes to retinal vascular cytolytic damage in DR is not well understood. In this study, we demonstrate that IgG-laden extracellular vesicles in rat plasma activate the classical complement pathway, and in vitro Streptozotocin (STZ)-induced rat diabetic plasma results in MAC deposition and cytolytic damage in human retinal endothelial cells (HRECs). Moreover, removal of the plasma extracellular vesicles reduced the MAC deposition and abrogated cytolytic damage seen in HRECs. Together, the results of this study demonstrate that complement activation by IgG-laden extracellular vesicles in plasma could lead to MAC deposition and contribute to endothelium damage and progression of DR.