title: Alterations in basement membrane immunoreactivity of the diabetic retina in three diabetic mouse models.
abstract: BACKGROUND
  The mouse retina contains three kinds of basement membrane (BM) structures; the inner limiting membrane (ILM), Bruch's membrane (BrM), and the BM surrounding the capillaries. We aimed to investigate possible variations of individual BM components and to detect effects caused by diabetes in three different diabetic mouse models.
  
  
  METHODS
  After 4 and 6 months of diabetes (defined by blood glucose > 250 mg/dl), we analyzed by immunohistochemistry the laminin, collagen IV, and nidogen-1 and nidogen-2 protein composition of the BMs obtained from diabetic and non-diabetic Leptin-receptor deficient (db/db) mice and insulin receptor (IR)/insulin receptor substrate-1 (IRS-1) double heterozygous knockout mice. In addition, C57BL/6 J mice were rendered diabetic by intraperitoneal injections of streptozotocin (STZ).
  
  
  RESULTS
  All analyzed BM proteins were detected in all of the three BMs with the exception of collagen IV, which was not detectable in the ILM of db/db mice and IR/IRS-1 mice. We present the first analysis of nidogen expression in diabetic BM. The staining patterns did not differ between the type-1 diabetic model (STZ) or the type-2 diabetic models (db/db and IR/IRS-1) and the wild-type controls, with only one exception: both the db/db mice and the IR/IRS-1 mice but not the STZ mice showed a decreased nidogen-1 immunoreactivity in the BrM after 4 months of diabetes, but not after 6 months.
  
  
  CONCLUSIONS
  The BMs in the three mouse strains differ with regard to protein immunoreactivity in the inner limiting membrane. Changes in BM composition may affect both the assembly and the function of the retinal BM. However, there are no marked differences in the BM composition between type-1 and type-2 diabetes. These results provide evidence for BM remodelling during diabetic retinopathy.
authors.affiliation: Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Abari
authors.forename: N
authors.initials: N
authors.lastname: Kociok
authors.forename: U
authors.initials: U
authors.lastname: Hartmann
authors.forename: I
authors.initials: I
authors.lastname: Semkova
authors.forename: M
authors.initials: M
authors.lastname: Paulsson
authors.forename: A
authors.initials: A
authors.lastname: Lo
authors.forename: A M
authors.initials: AM
authors.lastname: Joussen
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D007797:Laminin / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence
chemical_list: D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D007797:Laminin; D008562:Membrane Glycoproteins; C112846:Nid2 protein, mouse; C029967:nidogen