Aqueous Humor Cytokines in Non-Proliferative Diabetic Retinopathy

Medicina (Kaunas). 2022 Jul 8;58(7):909. doi: 10.3390/medicina58070909.

Abstract

Background and Objectives: Cytokines are cell-signaling proteins whose identification may serve as inflammatory markers or early indicators for progressive disease. The aim of our study was to quantify several cytokines in aqueous humor (AH) and their correlations with biochemical parameters in diabetic eyes with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: A total of 62 eyes from 62 patients were included in the study: 37 eyes from nondiabetic patients (group 1), 13 diabetic eyes with no retinopathy changes (group 2) and 12 diabetic eyes with early and moderate NPDR (group 3). AH samples were collected during uneventful cataract surgery. The cytokines IL-1β, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, TNF-α and VEGF were quantified using multiplex bead-based immunoassay. Due to unreliable results, IL-1β, TNF-α, IL-10 and IL-12 were excluded. Concentrations were compared between groups. Biochemical parameters (fasting blood sugar, glycated hemoglobin, C-reactive protein) and the duration of diabetes were recorded. Results: VEGF levels were significantly different between groups (p = 0.001), while levels of IL-6, IL-8, IP-10 and MCP-1 were comparable across all groups (p > 0.05). IL-6 concentration correlated with VEGF in group 1 (rho = 0.651, p = 0.003) and group 3 (rho = 0.857, p = 0.007); no correlation could be proved between IL-6, IL-8, IP-10, MCP-1 or VEGF and biochemical parameters. Duration of diabetes was not correlated with the cytokine levels in groups 2 and 3. The receiver operating characteristic (ROC) curve revealed that VEGF concentrations could discriminate early and moderate NPDR from diabetes, with an area under the curve (AUC) of 0.897 (p = 0.001, 95% CI = 0.74−1.0). Conclusions: Diabetes mellitus induces significant intraocular changes in the VEGF expression in diabetic patients vs. normal subjects, even before proliferative complications appear. VEGF was increasingly expressed once the diabetes progressed from no retinopathy to early or moderate retinopathy.

Keywords: VEGF; aqueous humor; cytokine biomarker; non-proliferative diabetic retinopathy.

MeSH terms

  • Aqueous Humor / metabolism
  • Chemokine CXCL10 / metabolism
  • Cytokines
  • Diabetes Mellitus*
  • Diabetic Retinopathy* / etiology
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-12
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Chemokine CXCL10
  • Cytokines
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • Interleukin-12

Grants and funding

This research received no external funding.