title: Fuchs Endothelial Corneal Dystrophy: A Systematic Immunofluorescence Study of Collagen Type VIII Suggests Heterogeneous Pathophysiology.
abstract: OBJECTIVE
  The purpose of this study was to investigate the pathophysiologic heterogeneity of Fuchs endothelial corneal dystrophy (FECD).
  
  
  METHODS
  We conducted a systematic immunofluorescence study on 39 Descemet membrane samples from FECD patients and compared these with 10 Descemet membrane samples from patients with pseudophakic bullous keratopathy (PBK) and 7 normal corneas. Samples were analyzed with immunofluorescence using antibodies to the α1-chain [collagen VIII α1-chain (COL8A1)] and α2-chain (COL8A2). Intensity of staining was assessed using a subjective grading scale from 0 to 3. The presence of specific staining patterns was noted.
  
  
  RESULTS
  The overall distribution of COL8A1 staining intensity between groups was significantly different (P = 0.002). There was marked/intense staining in 85% (33/39) of the FECD samples, 40% (4/10) of the PBK samples (P = 0.034), and 29% (2/7) of normal samples (P = 0.004). The overall distribution of COL8A2 staining intensity was not significantly different between groups (P = 0.39). There was marked/intense staining in 33% (13/39) of the FECD samples, 10% (1/10) of PBK samples, and 14% (1/7) of the normal samples. There was substantial variation in staining intensity in the FECD group, a phenomenon that was especially pronounced for the COL8A2 antibody.
  
  
  CONCLUSIONS
  We found increased staining for COL8A1, but not COL8A2 in FECD samples. Further, there was striking variation of staining intensity in FECD patients, indicating pathophysiological heterogeneity.
authors.affiliation: *Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark; and †Department of Medicine, University of Otago, Wellington, New Zealand. N. S. Greenhill and P. F. Davis are now with Trinity Bioactives Ltd, Gracefield, Lower Hutt, New Zealand.
authors.forename: Esben
authors.initials: E
authors.lastname: Nielsen
authors.forename: Kim
authors.initials: K
authors.lastname: Nielsen
authors.forename: Anders
authors.initials: A
authors.lastname: Ivarsen
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Greenhill
authors.forename: Paul F
authors.initials: PF
authors.lastname: Davis
authors.forename: Jesper
authors.initials: J
authors.lastname: Hjortdal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D024102:Collagen Type VIII / Q000378:metabolism*; D003886:Descemet Membrane / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005642:Fuchs' Endothelial Dystrophy / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C443712:COL8A2 protein, human; D024102:Collagen Type VIII