Role of CYP1B1 in glaucoma

Annu Rev Pharmacol Toxicol. 2008:48:333-58. doi: 10.1146/annurev.pharmtox.48.061807.154729.

Abstract

Glaucoma is a leading cause of blindness, estimated to affect 60 million people by 2010, and represents a heterogeneous group of neurodegenerative disease. The two major types of glaucoma include primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG). A genetically heterogeneous group of developmental disorders known as anterior segment dysgenesis (ASD) have been reported to be associated with increased intraocular pressure (IOP) and glaucoma. These include Peters' anomaly, Rieger's anomaly, aniridia, iris hypoplasia, and iridogoniodysgenesis. Genetic linkage analysis and mutation studies have identified CYP1B1 as a causative gene in PCG, as a modifier gene in POAG, and, on rare occasions, as causative gene in POAG as well as in several ASD disorders. CYP1B1-deficient mice exhibit abnormalities in their ocular drainage structure and trabecular meshwork that are similar to those reported in human PCG patients. Accordingly, it is speculated that diminished or absent metabolism of key endogenous CYP1B1 substrates adversely affects the development of the trabecular meshwork. CYP1B1 protein is involved in the metabolism of steroids, retinol and retinal, arachidonate, and melatonin. The conserved expression of CYP1B1 in both murine and human eyes, its higher expression in fetal than adult eyes, and its biochemical properties are consistent with this hypothesis. The exact role of CYP1B1 in the pathogenesis of glaucoma and other ASD disorders remains to be elucidated.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anterior Eye Segment / abnormalities
  • Anterior Eye Segment / physiopathology
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Cytochrome P-450 CYP1B1
  • Disease Models, Animal
  • Gene Expression
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / physiopathology
  • Humans
  • Mice
  • Mutation
  • Steroids / metabolism*

Substances

  • Steroids
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cyp1b1 protein, mouse
  • Cytochrome P-450 CYP1B1