title: Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis.
abstract: OBJECTIVE
  The ocular fundi of many patients with membranoproliferative glomerulonephritis type II (MPGN-II) are characterised by the presence of deposits within Bruch's membrane that resemble drusen, hallmark lesions associated with age-related macular degeneration (AMD). Glomerulonephritis (GN)-associated drusen appear at a younger age, however, than do drusen in individuals with AMD. In light of recent evidence that immune-mediated events participate in drusen biogenesis and AMD, we examined the structure and composition of drusen in eyes obtained from human donors with two distinct glomerulopathies, both of which involve complement deposition within glomeruli. These features were compared with those of drusen from patients with clinically documented AMD.
  
  
  METHODS
  Eyes obtained from two human human donors diagnosed with membranous and post-streptococcal GN, respectively, were analysed histochemically, immunohistochemically and ultrastructurally.
  
  
  RESULTS
  Subretinal pigment epithelial (RPE) deposits in both types of GN are numerous and indistinguishable, both structurally and compositionally, from drusen in donors with AMD. GN-associated drusen exhibit sudanophilia, bind filipin, and react with antibodies directed against vitronectin, complement C5 and C5b-9 complexes, TIMP-3 and amyloid P component. Drusen from the membranous GN donor, but not the post-streptococcal GN donor, reacted with peanut agglutinin and antibodies directed against MHC class II antigens and IgG. The ultrastructural characteristics of these deposits were also identical with those of AMD-associated drusen.
  
  
  CONCLUSIONS
  The composition and structure of ocular drusen associated with membranous and post-streptococcal/segmental GN are generally similar to those of drusen in individuals with AMD. In view of the recent data supporting the involvement of complement activation in drusen biogenesis and the pathobiology of AMD, further studies of the biological relationships between AMD and diseases associated with complement activation are warranted.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City 52240, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Mullins
authors.forename: N
authors.initials: N
authors.lastname: Aptsiauri
authors.forename: G S
authors.initials: GS
authors.lastname: Hageman
mesh_terms: D003167:Complement Activation; D005921:Glomerulonephritis / Q000150:complications*; D015433:Glomerulonephritis, Membranous / Q000150:complications; D006801:Humans; D007124:Immunoenzyme Techniques; D008268:Macular Degeneration / Q000150:complications; D008854:Microscopy, Electron; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000648:ultrastructure; D015593:Retinal Drusen / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D013290:Streptococcal Infections / Q000150:complications