title: Changes to tear cytokines of type 2 diabetic patients with or without retinopathy.
abstract: OBJECTIVE
  To investigate changes in cytokine levels in tears of type 2 diabetics with or without retinopathy.
  
  
  METHODS
  Tears were collected from 15 type 2 diabetics without retinopathy (DNR), 15 patients with retinopathy (DR), and 15 age and gender matched non-diabetic controls. Tear concentrations of 27 cytokines were measured by multiplex bead immunoassay. Cytokine differences between groups, ratios of type-1 T helper (Th1)/type-2 T helper (Th2) cytokines and anti-angiogenic/pro-angiogenic cytokines were analyzed statistically.
  
  
  RESULTS
  The most abundant cytokine detected in tears was interferon-induced protein-10 (IP-10). In comparison with controls, IP-10 and monocyte chemoattracant protein-1 (MCP-1) levels were significantly elevated in DR (p=0.016 and 0.036, respectively) and DNR groups (p=0.021 and 0.026, respectively). Interleukin-1 (IL-1) receptor antagonist (IL-1ra) levels were significantly increased in DNR (p=0.016). Th1/Th2 cytokines interferon-gamma (IFN-γ)/IL-5 and IL-2/IL-5 ratios were significantly increased in DR compared to controls (p=0.037 and 0.031, respectively). Anti-angiogenic/angiogenic cytokines IFN-γ/MCP-1 and IL-4/MCP-1 ratios in DR and DNR were significantly decreased compared to controls (p<0.05). IL-4/IL-8 and IL-12p70/IL-8 ratios were also significantly decreased in DR compared to controls (p=0.02 and 0.045, respectively). No significant correlation was demonstrated between tear cytokine concentrations and glycosylated hemoglobin (HbA1c) or fasting plasma glucose (FPG).
  
  
  CONCLUSIONS
  Diabetic tears exhibited elevated levels of IP-10 and MCP-1. The Th1/Th2 cytokine balance may shift to a predominantly Th1 state in DR patients. Pro-angiogenic cytokines are more highly represented than anti-angiogenic cytokines in the tears of diabetic patients.
authors.affiliation: First Hospital Affiliated to Medical College, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jingfang
authors.initials: J
authors.lastname: Liu
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.forename: Shuixiang
authors.initials: S
authors.lastname: He
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yao
authors.forename: Mark D P
authors.initials: MD
authors.lastname: Willcox
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000276:immunology*; D003930:Diabetic Retinopathy / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013666:Tears / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D016207:Cytokines; D007070:Immunoglobulin A