Cytochrome P450 1B1 and Primary Congenital Glaucoma

Abstract

Cytochrome P450 1B1 (Cyp1b1) belongs to the CYP450 superfamily of heme-binding mono-oxygenases which catalyze oxidation of various endogenous and exogenous substrates. The expression of Cyp1b1 plays an important role in the modulation of development and functions of the trabecular meshwork (TM). Mutations in Cyp1b1 have been reported in patients with primary congenital glaucoma (PCG). Mice lacking Cyp1b1 also exhibit developmental defects in the TM similar to those reported in congenital glaucoma patients. However, how Cyp1b1 deficiency contributes to TM dysgenesis remains unknown. In the present review, we will address the significance of Cyp1b1 expression and/or its function in anterior segment development. Cyp1b1-deficient (Cyp1b1 (-/-)) mice are discussed as a promising model for an oxidative stress-induced model of PCG, in which Cyp1b1 activity is revealed as an important modulator of oxidative homeostasis contributing to the development and structural function of the TM. This conclusion suggests a possible clinical intervention for individuals who are genetically at high risk of developing PCG.

Keywords: Anterior Chamber; Cyp1b1; Oxidative Stress; Periostin; Trabecular Meshwork.

Figure 1

The wild-type and mutant forms of the molecule. (a) The wild-type is anchored on the membrane of the endoplasmic reticulum. With the help of P450 reductase as a redox partner, CYP450s insert an atom of molecular oxygen into their substrates. (b) The sites of critical missense mutations in CYP1B1. B, C, E and F stands for B-, C-, E-and F-helices. CCS, conserved core structure. (c) The truncating or missense mutations of CYP1B1 highly affect conserved amino acid residues located predominantly in either the hinge region or the CCS part of the protein. CCS, conserved core structures.