Differential accumulation of advanced glycation end products in the course of diabetic retinopathy

Diabetologia. 1999 Jun;42(6):728-36. doi: 10.1007/s001250051221.


Aims/hypothesis: Glycated proteins, formed by reaction of glucose and protein, react further yielding numerous, mostly undefined advanced glycation end products (AGE). The recently characterized imidazolone-type AGE (AG-1) is non-oxidatively formed involving 3-deoxyglucosone whereas some AGEs, particularly N(epsilon)-(carboxymethyl)lysine (CML), are formed only in the presence of oxygen.

Methods: To study the possible contribution of oxidative and non-oxidative AGE formation in the development of diabetic retinopathy antibodies directed against CML-type and imidazolone-type AGEs were characterized by dot blot analysis and used to localize these well-characterized epitops in the retinas from diabetic rats (early course) and from human Type I (insulin-dependent) diabetes mellitus with laser-treated proliferative diabetic retinopathy (late course).

Results: In non-diabetic rats CML was moderately positive in neuroglial and vascular structures of non-diabetic rat retinas and increased strongly in diabetic retinas. Anti-imidiazolone antibody staining was strongly positive only in diabetic capillaries. Advanced human diabetic retinopathy showed strong CML-immunolabelling of the entire retina whereas control samples showed moderate staining of neuroglial structures only with the polyclonal CML-antibody. Anti-imidiazolone antibody staining was faint in the inner retina of control sections but were strong throughout the entire diabetic retina. Immunolabelling for the AGE-receptor was congruent with a marker of Müller cells.

Conclusion/interpretation: Our data indicate that the oxidatively formed CML is present in non-diabetic retinas as a regular constituent but increases in diabetes both in neuroglial and vascular components. Imidazolone-type AGE are restricted to microvessels and spread during later stages over the entire retina, co-localizing with the expression of AGE-receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / pathology
  • Glycation End Products, Advanced / metabolism*
  • Humans
  • Immunohistochemistry
  • Membrane Proteins / metabolism
  • Rats
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism
  • Retina / metabolism


  • Glycation End Products, Advanced
  • Membrane Proteins
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic