Assessment of biomarkers using multiplex assays in aqueous humor of patients with diabetic retinopathy

Abstract

BackgroundWith the high prevalence of type 2 diabetes, diabetic retinopathy (DR) has become a leading health problem worldwide. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. The purpose of this study was to assess the levels of immune and inflammatory biomarkers in the aqueous humor of patients with different severities of DR and to analyze the correlations between Interleukin-6 (IL-6) and these biomarkers, and between IL-6 and the severity of the disease.MethodsAqueous humor samples were obtained from 51 non-diabetic patients and 151 diabetic patients. Levels of 45 different cytokines, chemokines, and growth factors were measured using a multiplex bead immunoassay.ResultsIL-6, IL-8, Inducible Protein-10 (IP-10), leukemia inhibitory factor (LIF), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF)-A were significantly higher (p < 0.05) in the aqueous humor of the DR patients compared to the non-diabetic patients, while the concentrations of IL-1α, IL-4, IL-9, IL-21, IL-23, IL-27, IL-31, RANTES, interferon-α, growth regulated oncogene (GRO), and tumor necrosis factor (TNF)-α were significantly lower (p < 0.05) in the DR patients. The IL-6 levels increased as the severity of DR increased. In addition, the IL-6 level positively correlated with the IL-8, HGF and LIF levels, while negatively with the IL-31and GRO levels.ConclusionsThese findings suggest that inflammation and immune response may contribute to the pathogenesis of DR, and these biomarkers may potentially be new therapeutic targets for DR.

Relationship between aqueous humor cytokine level changes and retinal vascular changes after intravitreal aflibercept for diabetic macular edema

“…Several studies investigating the intraocular concentrations of cytokines have revealed the relations between vitreous or humor aqueous levels of VEGF, IL-6, IL-8, inducible protein-10 (IP-10), intercellular adhesion molecule 1 (ICAM-1) and monocyte chemotactic protein 1 (MCP-1) and DME 3 – 6 .…”

Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy

“…Elevated levels of IL-6 have been reported to participate as a proinflammatory and angiogenic factor in PDR and DM, is also involved in crossing both the blood-brain barrier and the blood-retinal barrier [189,190], and their levels in DR patients increased significantly compared to those in a non-diabetic control group. IL-6 levels were significantly correlated with PDR and it can act as one of the main drivers to generate a change in the cytokine profile in the aqueous humor of DR patients [115,191].…”

“…Lactotransferrin (LTF) and Immunoglobulin λ are increased in PDR together with another tear proteins expressed with frequency in PDR like lipocalin 1 (LCN1), lysozyme C (LYZ), lipophilin A, lacritin (LACRT) lipidic carriers for retinoids required for tear production, their increase are specifically associated as predictors for DR progression, some are linked to inflammation secondary to neovascularization, bleeding or macular edema [188]. Interestingly, IL-6 levels were positively correlated with the DR stage (PDR: 47.68 vs. NPDR: 29.68 pg/mL; p < 0.001) [115]. Elevated levels of IL-6 have been reported to participate as a proinflammatory and angiogenic factor in PDR and DM, is also involved in crossing both the blood-brain barrier and the blood-retinal barrier [189,190], and their levels in DR patients increased significantly compared to those in a non-diabetic control group.…”

“…IL-8 is an important chemoattractant that regulates chronic leukocytic inflammation in the vascular walls and ultimately leads to capillary occlusion and retinal ischemia [193], its levels have been reported in the AH of DR patients with 42.20 ± 33.03 pg/mL (mean ± SD) [115]. IL-8 expression can be hypoxia-induced and mediated by nuclear factor kappa B (NF-kB).…”

Endocannabinoids in aqueous humour of patients with or without diabetes

“…It is the leading cause of blindness among individuals aged 20–74 years in the UK,2 with nearly all patients with type 1 diabetes and >60% of patients with type 2 diabetes having some form of retinopathy by the first decade of diabetes 3 4. Vascular endothelial growth factor (VEGF) and other inflammatory mediators induced by hyperglycaemia and ischaemia are instrumental in developing diabetic retinopathy,2 5 6 and intravitreal anti-VEGF biologics, steroid implants and retinal laser photocoagulation remain the mainstay of treatment 7. However, as many patients remain visually impaired, further knowledge of novel substances or growth factors associated with ischaemia-induced angiogenesis is important as we seek novel therapeutic strategies to treat and prevent STDR.…”