Vitreous inflammatory and angiogenic factors on patients with proliferative diabetic retinopathy or diabetic macular edema: the role of Lipocalin2

PURPOSE: Quantitative analysis of vitreous inflammatory and angiogenic factors from patients with proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). MATERIALS AND METHODS: Collection of undiluted vitreous samples from 20 diabetic patients: 13 with proliferative diabetic retinopathy (PDR) and 7 with diabetic macular edema (DME). DME patients had suboptimal response to anti-VEGF treatment. Samples from 11 control patients, with vitreomacular interface pathology such as idiopathic epiretinal membrane (iERM) (n = 4), vitreomacular traction syndrome (VMT) (n = 3) and full thickness macular hole (FTMH) (n = 3), were also collected. The levels of IL1b, IL6, IL8, IL27, TNFα, ICAM-1, VCAM, MCP-1, VEGFA and LCN2 were measured using cytometry flow analysis. Median values were compared with Mann–Whitney test since the distributions were skewed. Statistical analysis was performed with the Statistical Package for Social Sciences software (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). RESULTS: The median concentration of LCN2, IL6, IL8, IL1b, IL27, ICAM, VCAM-1, MCP-1, TNFa and VEGFA was higher in PDR patients than in controls. Similarly, the median concentration of LCN2, IL6, IL8, IL27, ICAM, VCAM-1, TNFa and VEGFA was higher in DME patients than in controls. In particular, median LCN2 concentration in diabetic patients was 5,711 pg/ml (interquartile range [IR] = 2,534), while in controls was 2,586 pg/ml (IR = 2,345). Moreover, median LCN2 was 6,534 pg/ml in the DME group (IR = 6,850) and 4,785 pg/ml in the PDR group (IR = 2,608), (p = 0.025). CONCLUSION: Various inflammatory and angiogenic factors are involved in the pathophysiology of PDR and DME. Elevated vitreous levels of LCN2 in PDR and especially in DME patients reveal a potential pathogenic association. More extended studies could verify LCN2 as an alternative therapeutic target.