Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway

Diabetes. 2018 Aug;67(8):1639-1649. doi: 10.2337/db17-1587. Epub 2018 Jun 4.

Abstract

Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in working-age adults. Recent studies have implicated the complement system as a player in the development of vascular damage and progression of DR. However, the role and activation of the complement system in DR are not well understood. Exosomes, small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma, suggesting that they can participate in causing the vascular damage associated with DR. We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway and that the quantity of these exosomes is increased in diabetes. Moreover, we show that a lack of IgG in exosomes in diabetic mice results in a reduction in retinal vascular damage. The results of this study demonstrate that complement activation by IgG-laden plasma exosomes could contribute to the development of DR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Capillary Permeability
  • Centrifugation, Density Gradient
  • Complement Activation*
  • Complement System Proteins / analysis
  • Complement System Proteins / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / physiopathology
  • Disease Progression
  • Exosomes / immunology
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Immunoglobulin G / analysis
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Microvessels / immunology
  • Microvessels / metabolism
  • Microvessels / pathology
  • Microvessels / physiopathology*
  • Retina / immunology
  • Retina / metabolism
  • Retina / pathology
  • Retina / physiopathology*
  • Retinal Vessels / immunology
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology
  • Retinal Vessels / physiopathology*
  • Ultracentrifugation

Substances

  • Biomarkers
  • Immunoglobulin G
  • Complement System Proteins