Profile of Lipid and Protein Autacoids in Diabetic Vitreous Correlates With the Progression of Diabetic Retinopathy

Abstract

OBJECTIVEThis 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.RESEARCH DESIGN AND METHODSVitreous 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.RESULTSVitreous 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)-α. 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.CONCLUSIONSThis 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.

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

“…5e8 Numerous studies have linked the overexpression of proinflammatory factors as an underlying cause of lowgrade inflammation. 5,9,10 Among these factors, the IL-1 subfamily of cytokines, consisting IL-1a, IL-1b, and IL-1 receptor antagonist (IL-1Ra, encoded by gene IL1RN in the humans), have attracted much attention because they have been implicated as a cause for the pathoencodesis of both type 1 11,12 and type 2 diabetes 13 and linked to complications with low-grade inflammation as a root cause. 8,14 IL-1 type cytokines are major mediators of inflammatory and innate immune reactions, and blockade of IL-1a and IL-1b by IL-1Ra has demonstrated a central role of IL-1 in several human autoinflammatory diseases, including rheumatoid arthritis and gout, and autoinflammatory syndromes.…”

Optical quality of the diabetic eye: a review

“…64 As disease progresses, angiogenic factors that induce the growth of new retinal blood vessels (neovascularization) are secreted. 65 Yokoi et al 66 found that the vitreous levels of AGEs and vascular endothelial growth factor (VEGF) correlate with each other, both of which are inversely associated with vitreous total antioxidant capacity in patients with DR. Kinnunen et al 67 showed differences in growth factor expression between people with type 1 and type 2 DM with retinopathy, while VEGF-A was most abundantly present in type 1 DM, and VEGF-D was more copious in the neovascular tissues of patients with type 2 DM. They suggested the possibility that an inflammatory mechanism accelerates proliferative retinopathy in type 2, by VEGF-D-dependent pathways, and type 1 DM hypoxia is more important in the development of proliferative retinopathy than inflammation.…”

Biomarkers in Diabetic Retinopathy

“…2. 'Omics' studies, including proteomics [27,28] and lipidomics [29], which are beginning to be applied to diabetic retinopathy.…”