Aqueous humour concentrations of TGF-β, PLGF and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy

Acta Ophthalmol. 2017 May;95(3):e206-e211. doi: 10.1111/aos.13230. Epub 2016 Sep 28.


Purpose: To correlate angiogenic cytokines in the aqueous humour with total retinal blood flow in subjects with type 2 diabetes with non-proliferative diabetic retinopathy (NPDR).

Methods: A total of 17 controls and 16 NPDR patients were recruited into the study. Aqueous humour was collected at the start of cataract surgery to assess the concentration of 14 angiogenic cytokines. Aqueous humour was analysed using the suspension array method. Six images were acquired to assess total retinal blood flow (TRBF) using the prototype RTVue Doppler Fourier domain optical coherence tomography (Doppler FD-OCT) (Optovue, Inc., Fremont, CA) using a double circular scan protocol, 1 month postsurgery. At the same visit, forearm blood was collected to determine glycosylated haemoglobin (A1c).

Results: Transforming growth factor beta (TGF-β1, TGF-β2) and PLGF were increased while FGF-1 was reduced in NPDR compared to controls (Bonferroni corrected, p < 0.003 for all). Total retinal blood flow (TRBF) was significantly reduced in the NPDR group compared to controls (33.1 ± 9.9 versus 43.3 ± 5.3 μl/min, p = 0.002). Aqueous FGF-1 significantly correlated with TRBF in the NPDR group (r = 0.71, p = 0.01; r2 = 0.51). In a multiple regression analysis, A1c was found to be a significant predictor of aqueous TGF-β1 and FGF-1 (p = 0.018 and p = 0.020, respectively).

Conclusion: Aqueous angiogenic cytokines (TGF-β1, TGF-β2 and PLGF) were elevated in conjunction with a reduction in TRBF in patients with NPDR compared to controls. Non-invasive measurement of TRBF may be useful for predicting aqueous FGF-1 levels and severity of vasculopathy in DR.

Keywords: angiogenesis; aqueous humour cytokines; fibroblast growth factor; non-proliferative diabetic retinopathy; optical coherence tomography; retinal blood flow; type 2 diabetes mellitus; vasoregulatory.

MeSH terms

  • Aged
  • Aqueous Humor / metabolism*
  • Biomarkers / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Retinopathy / diagnosis
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / physiopathology
  • Female
  • Fibroblast Growth Factor 1 / metabolism*
  • Humans
  • Male
  • Placenta Growth Factor / metabolism*
  • Regional Blood Flow / physiology*
  • Retinal Vessels / diagnostic imaging
  • Retinal Vessels / physiopathology*
  • Tomography, Optical Coherence / methods
  • Transforming Growth Factor beta / metabolism*


  • Biomarkers
  • PGF protein, human
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 1
  • Placenta Growth Factor