Role of ox-LDL immunocomplexes in diabetic retinopathy

Wu, Mingyuan; Chen, Y.; Abdelsamie, Souzan A.; Wilson, Ken; Boulton, Michael E.; Ma, Jian-Xing; Virella, G.; Lopes‐Virella, Maria F.; Lyons, Timothy

doi:10.1016/s1499-2671(09)33102-0

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“…Among all the modified proteins that can emerge as a consequence of glycoxidation and lipid peroxidation, LDL seems to be particularly important. As increased permeability in retinal vessels develops in early retinopathy, oxLDL and AGE-LDL IgG antibodies can diffuse to the extravascular space, thus favoring the formation of proinflammatory ICs in the vessel walls in the retina; indeed we have shown that oxLDL-ICs are present in diabetic retina but not in normal retina ( 28 ). Also, recent in vitro work has shown that oxLDL-ICs lead to pericyte loss, one of the initial steps in the development of retinopathy.…”

Section: Discussionmentioning

confidence: 73%

High Concentrations of AGE-LDL and Oxidized LDL in Circulating Immune Complexes Are Associated With Progression of Retinopathy in Type 1 Diabetes

Lopes‐Virella

Baker²,

Hunt³

et al. 2012

Diabetes Care

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OBJECTIVETo determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)–LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes.RESEARCH DESIGN AND METHODSLevels of AGE-LDL and oxLDL in ICs were measured in 517 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression.RESULTSIn unadjusted models, higher baseline levels of AGE-LDL-ICs and oxLDL-ICs significantly predicted progression of diabetic retinopathy outcomes. After adjustment by study-design variables (treatment group, retinopathy cohort, duration of type 1 diabetes, and baseline albumin excretion rate [AER], hemoglobin A1c (HbA1c), and Early Treatment Diabetic Retinopathy Study [ETDRS] score), one SD increase in IC levels was associated with 47% (hazard ratio [HR] 1.47 [95% CI 1.19–1.81]; AGE-LDL-IC) and 45% (1.45 [1.17–1.80]; oxLDL-IC) increased risk of developing proliferative diabetic retinopathy (PDR) and 37% (1.37 [1.12–1.66]; to both ICs) increased risk of progressing to severe nonproliferative retinopathy. Analyses were stratified by retinopathy cohort because results differed between primary and secondary cohorts. For AGE-LDL-ICs, HR for progression to PDR was 2.38 (95% CI 1.30–4.34) in the primary cohort and attenuated in the secondary cohort (1.29 [1.03–1.62]). Similar results were observed for oxLDL-ICs.CONCLUSIONSIncreased levels of AGE-LDL and oxLDL in ICs are associated with increased risk for progression to advanced retinopathy in patients with type 1 diabetes, indicating that the antibody response to modified LDL plays a significant role in retinopathy progression.

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Section: Discussionmentioning

confidence: 73%