Role of hyperglycemia-mediated erythrocyte redox state alteration in the development of diabetic retinopathy

Retina. 2013 Jan;33(1):207-16. doi: 10.1097/IAE.0b013e318256202e.

Abstract

Purpose: To evaluate erythrocyte redox state and its surrogates in patients with different stages of diabetic retinopathy and their association with cellular metabolic derangement developed in retinal microvascular cells.

Methods: Sixty type 2 diabetic patients with nonproliferative diabetic retinopathy (NPDR), 85 patients with proliferative diabetic retinopathy (PDR), and 70 patients with diabetes but without retinopathy were considered as diabetic control (DC) for the study. In addition, 65 normal individuals without diabetes were enrolled as healthy control in this study. Erythrocyte oxidized nicotinamide adenine dinucleotide phosphate / reduced nicotinamide adenine dinucleotide phosphate (NADP / NADPH), oxidized nicotinamide adenine dinucleotide / reduced nicotinamide adenine dinucleotide (NAD / NADH) glutathione, plasma and vitreous lactate, and pyruvate levels were determined by enzymatic reaction-based spectrophotometric assay for the patients and individuals.

Result: Erythrocyte NADP+ to NADPH ratio to NADPH ratio was found to be significantly higher among NPDR and PDR patients compared with DC subjects (P < 0.0001). Erythrocyte-reduced glutathione was significantly decreased in patients of NPDR (P = 0.0004) and patients of PDR (P = 0.0157) compared to DC. Erythrocyte NAD to NADH ratio was also significantly decreased in patients of NPDR (P < 0.0001) and PDR (P < 0.0001) compared to DC subjects. Lactate to pyruvate ratio of plasma was elevated significantly in patients with NPDR compared with DC (P < 0.0001) and those having PDR (P = 0.0046). In the vitreous fluid, the lactate to pyruvate ratios were found to be significantly lower in normal individuals without diabetes compared with patients having PDR (P < 0.0001).

Conclusion: Hyperglycemia-mediated erythrocyte redox state alterations might be a potential risk factor for the development of NPDR in poorly controlled diabetic subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism
  • Blood Pressure
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetic Retinopathy / blood*
  • Erythrocyte Membrane / metabolism
  • Erythrocytes / metabolism*
  • Female
  • Fluorescein Angiography
  • Glucose Tolerance Test
  • Glutathione / metabolism
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hyperglycemia / blood*
  • Lactic Acid / blood
  • Male
  • Middle Aged
  • NAD / metabolism*
  • NADP / metabolism*
  • Oxidation-Reduction
  • Pyruvic Acid / blood

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • NAD
  • Lactic Acid
  • NADP
  • Pyruvic Acid
  • Glutathione