Oxidative stress-associated neuroretinal dysfunction and nitrosative stress in diabetic retinopathy

Can J Diabetes. 2013 Dec;37(6):401-7. doi: 10.1016/j.jcjd.2013.05.004.

Abstract

Objective: The present study was intended to investigate whether oxidative stress is the key regulator to alter neuroretinal biochemical homeostasis and in turn aggravate the process of diabetic retinopathy by inducing nitrosative stress in the retinal neurovascular unit.

Methods: Peripheral blood mononuclear cell reactive oxygen species level was measured by flow cytometry along with spectrophotometric detection of malondialdehyde (MDA) and glutamate from serum or plasma and a vitreous sample of study groups (i.e. subjects with proliferative diabetic retinopathy [PDR], type 2 diabetes without retinopathy [DNR] and healthy controls [HCs]). Further, nitrosative stress assessment was performed by spectrophotometric and enzyme-linked immunosorbent assay-based detection of serum and vitreous nitrite and nitrotyrosine concentrations, respectively.

Results: The plasma glutamate level remains insignificant between subjects with PDR and DNR (p=0.505) or in HC (p=0.1344) individuals. However, serum MDA (p=0.0004), nitrite (p=0.0147) and nitrotyrosine (p=0.0129) were found to be strikingly higher among PDR subjects compared with the DNR group. Significantly increased levels of peripheral blood mononuclear cell reactive oxygen species (p<0.0001), vitreous glutamate (p=0.0009, p<0.0001), MDA (p=0.0058, p=0.0003), nitrite (p=0.0014, p<0.0001) and nitrotyrosine (p=0.0008, p<0.0001) were found in PDR subjects compared with DNR and HC subjects, respectively.

Conclusions: Our observation suggests that oxidative stress is associated with impairment in neuroretinal biochemical homeostasis among PDR subjects, which further augments retinal nitrosative stress and thus worsens the pathogenic process of retinopathy among PDR subjects.

Keywords: diabetic retinopathy; espèces réactives de l’oxygène (ERO); glutamate; nitrosative stress; oxidative stress; reactive oxygen species (ROS); rétinopathie diabétique; stress nitrosatif; stress oxydatif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / physiopathology
  • Female
  • Glutamic Acid / blood*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Middle Aged
  • Nitrites / blood
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Retina / metabolism*
  • Retina / physiopathology
  • Tyrosine / analogs & derivatives
  • Tyrosine / blood
  • Vitreous Body / metabolism*

Substances

  • Nitrites
  • Reactive Oxygen Species
  • 3-nitrotyrosine
  • Glutamic Acid
  • Tyrosine
  • Malondialdehyde