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

Autor: Kiera Fisher, Chao Huang, Julia V. Busik, Sandra S Hammer, Svetlana Navitskaya, Gary J. Blanchard
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Complications
Endocrinology
Diabetes and Metabolism

Vascular permeability
Exosomes
Retina
Diabetes Mellitus
Experimental

Capillary Permeability
03 medical and health sciences
Classical complement pathway
chemistry.chemical_compound
0302 clinical medicine
Microscopy
Electron
Transmission

Diabetes mellitus
Centrifugation
Density Gradient

Internal Medicine
medicine
Extracellular
Animals
Complement Activation
Mice
Knockout

Diabetic Retinopathy
business.industry
Retinal Vessels
Retinal
Complement System Proteins
Diabetic retinopathy
medicine.disease
Microvesicles
3. Good health
Complement system
Mice
Inbred C57BL

030104 developmental biology
Microscopy
Fluorescence

chemistry
Immunoglobulin G
030220 oncology & carcinogenesis
Microvessels
Disease Progression
Cancer research
business
Ultracentrifugation
Biomarkers
Zdroj: Diabetes
ISSN: 1939-327X
0012-1797
DOI: 10.2337/db17-1587
Popis: 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.
Databáze: OpenAIRE