title: Extensive deposits of complement C3d and C5b-9 in the choriocapillaris of eyes of patients with diabetic retinopathy.
abstract: OBJECTIVE
  To determine the presence of activated complement components in eyes affected by diabetic retinopathy.
  
  
  METHODS
  Eyes of 50 deceased donors with diabetic retinopathy and of 10 nondiabetic subjects with uveal melanoma (n = 6) or phthisical eyes (n = 4), as well as eyes of 16 deceased donors without diabetic retinopathy were subjected to immunohistochemical studies, using a panel of antibodies directed against candidate markers of complement activation.
  
  
  RESULTS
  Extensive deposits of complement C5b-9 complexes were detected in the choriocapillaris immediately underlying the Bruch membrane and densely surrounding the capillaries, in all 50 diabetic retinopathy specimens. Complement deposition was sometimes also observed around the larger choroidal vessels. Similarly intense staining for C5b-9 was absent in 25 of the 26 of the other donor eyes. Positive staining was observed in a case of systemic amyloidosis. Staining for C3d positively correlated with C5b-9 staining, corroborating the notion that complement activation had occurred in situ. Furthermore, positive staining was found for vitronectin, which forms stable complexes with extracellular C5b-9. When present, deposits under the pigment epithelium and drusen also stained positively for the activated complement components, independent of diabetic retinopathy. In contrast, there was no positive staining for C-reactive protein (CRP), mannose-binding lectin (MBL), C1q, or C4, indicating that complement activation did not occur through a C4-dependent pathway.
  
  
  CONCLUSIONS
  The presence of C3d, C5b-9, and vitronectin indicates that complement activation occurs to completion, possibly through the alternative pathway in the choriocapillaris in eyes affected by diabetic retinopathy. Complement activation at this site may evoke a spectrum of pathologic sequelae that could contribute to ocular tissue disease and visual impairment.
authors.affiliation: Department of Ophthalmology, University of Mainz, Mainz, Germany. sbhakdi@mail.uni-mainz.de
authors.forename: Verena B
authors.initials: VB
authors.lastname: Gerl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bohl
authors.forename: Susanne
authors.initials: S
authors.lastname: Pitz
authors.forename: Bernhard
authors.initials: B
authors.lastname: Stoffelns
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.forename: Sucharit
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D002196:Capillaries; D003167:Complement Activation / Q000502:physiology; D015933:Complement C3d / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000502:physiology; D003930:Diabetic Retinopathy / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000378:metabolism; D008875:Middle Aged; D012171:Retinal Vessels / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015938:Complement Membrane Attack Complex; D019096:Vitronectin; D015933:Complement C3d