title: The p.Gly61Glu Mutation in CYP1B1 Affects the Extracellular Matrix in Glaucoma Patients.
abstract: OBJECTIVE
  The aim of this work was to assess the possible effects of CYP1B1 mutations on the extracellular matrix (ECM) in glaucoma patients. CYP1B1 mutations are the cause of disease in a notable fraction of primary congenital glaucoma (PCG) patients and in a smaller fraction of primary open angle glaucoma (POAG) patients.
  
  
  METHODS
  The study was performed on a glaucoma family with the common homozygous p.Gly61Glu CYP1B1 mutation. The father was affected with POAG and three siblings had PCG. Microscopy was performed on the skin of the father and one son, as well as controls. Immunohistochemical studies were done using anti-CYP1B1 and anti-fibrillin-1 antibodies. Fibrillin-1 served as a marker for the ECM, and electron microscopy was also performed.
  
  
  RESULTS
  CYP1B1 expression patterns were the same in the patients and controls. However, microfibrils that are associated with fibrillin-1 were less abundant and more fragmented in both patients. Electron microscopy showed disturbed collagen fibers only in the PCG patient.
  
  
  CONCLUSIONS
  The p.Gly61Glu mutation in CYP1B1 affects the ECM structure. This implies that the ECM of the trabecular meshwork may also be disrupted in a manner that affects aqueous humor flow resulting in increased intraocular pressure and contributing to the glaucoma phenotype.
authors.affiliation: School of Biology, University College of Science, University of Tehran, Tehran, Iran.
authors.forename: Iman
authors.initials: I
authors.lastname: Safari
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Suri
authors.forename: Ramona
authors.initials: R
authors.lastname: Haji-Seyed-Javadi
authors.forename: Shahin
authors.initials: S
authors.lastname: Yazdani
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D000368:Aged; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
chemical_list: D004247:DNA; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1