Profile of lipid and protein autacoids in diabetic vitreous correlates with the progression of diabetic retinopathy.
OBJECTIVE
This study was aimed at obtaining a profile of lipids and proteins with a paracrine function in normal and diabetic vitreous and exploring whether the profile correlates with retinal pathology.


METHODS
Vitreous was recovered from 47 individuals undergoing vitreoretinal surgery: 16 had nonproliferative diabetic retinopathy (NPDR), 15 had proliferative diabetic retinopathy, 7 had retinal detachments, and 9 had epiretinal membranes. Protein and lipid autacoid profiles were determined by protein arrays and mass spectrometry-based lipidomics.


RESULTS
Vitreous lipids included lipoxygenase (LO)- and cytochrome P450 epoxygenase (CYP)-derived eicosanoids. The most prominent LO-derived eicosanoid was 5-hydroxyeicosate traenoic acid (HETE), which demonstrated a diabetes-specific increase (P = 0.027) with the highest increase in NPDR vitreous. Vitreous also contained CYP-derived epoxyeicosatrienoic acids; their levels were higher in nondiabetic than diabetic vitreous (P < 0.05). Among inflammatory, angiogenic, and angiostatic cytokines and chemokines, only vascular endothelial growth factor (VEGF) showed a significant diabetes-specific profile (P < 0.05), although a similar trend was noted for tumor necrosis factor (TNF)-alpha. Soluble VEGF receptors R1 and R2 were detected in all samples with lowest VEGF-R2 levels (P < 0.05) and higher ratio of VEGF to its receptors in NPDR and PDR vitreous.


CONCLUSIONS
This study is the first to demonstrate diabetes-specific changes in vitreous lipid autacoids including arachidonate and docosahexanoate-derived metabolites indicating an increase in inflammatory versus anti-inflammatory lipid mediators that correlated with increased levels of inflammatory and angiogenic proteins, further supporting the notion that inflammation plays a role the pathogenesis of this disease.
Schwartzman
Michal Laniado
ML
Department of Pharmacology, New York Medical College, Valhalla, New York, USA. michal_schwartzman@nymc.edu
Iserovich
Pavel
P
Gotlinger
Katherine
K
Bellner
Lars
L
Dunn
Michael W
MW
Sartore
Mauro
M
Grazia Pertile
Maria
M
Leonardi
Andrea
A
Sathe
Sonal
S
Beaton
Ann
A
Trieu
Lynn
L
Sack
Robert
R
D000368:Aged; D012898:Autacoids / Q000032:analysis* / Q000378:metabolism; D018925:Chemokines / Q000032:analysis* / Q000378:metabolism; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D018450:Disease Progression; D015777:Eicosanoids / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014822:Vitreous Body / Q000737:chemistry* / Q000378:metabolism
D012898:Autacoids; D018925:Chemokines; D016207:Cytokines; D015777:Eicosanoids