title: Differential accumulation of advanced glycation end products in the course of diabetic retinopathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Justus-Liebig-Universität Giessen, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Hammes
authors.forename: A
authors.initials: A
authors.lastname: Alt
authors.forename: T
authors.initials: T
authors.lastname: Niwa
authors.forename: J T
authors.initials: JT
authors.lastname: Clausen
authors.forename: R G
authors.initials: RG
authors.lastname: Bretzel
authors.forename: M
authors.initials: M
authors.lastname: Brownlee
authors.forename: E D
authors.initials: ED
authors.lastname: Schleicher
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012160:Retina / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic