Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin

J Clin Invest. 1998 Aug 15;102(4):783-91. doi: 10.1172/JCI2425.

Abstract

This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively (P < 0. 001). The number of surviving ganglion cells was also reduced by 10% compared to controls (P < 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in whole-mounted rat retinas after 1, 3, 6, and 12 months of diabetes (P < 0.001, P < 0. 001, P < 0.01, and P < 0.01, respectively). Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor. Insulin implants significantly reduced the number of TUNEL-positive cells (P < 0.05). The number of TUNEL-positive cells was also increased in retinas from humans with diabetes. These data indicate that retinal neural cell death occurs early in diabetes. This is the first quantitative report of an increase in neural cell apoptosis in the retina during diabetes, and indicates that neurodegeneration is an important component of diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Apoptosis*
  • Blood Glucose / analysis
  • Body Weight
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / pathology*
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Insulin / therapeutic use
  • Male
  • Middle Aged
  • Neuroglia / pathology
  • Neurons / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Degeneration / complications
  • Retinal Degeneration / pathology*
  • Retinal Ganglion Cells / pathology
  • Streptozocin

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Streptozocin