Zhao Yun, Sorenson Christine M, Sheibani Nader
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA ; McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
J Ophthalmic Vis Res. 2015 Jan-Mar;10(1):60-7. doi: 10.4103/2008-322X.156116.
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.
细胞色素P450 1B1(Cyp1b1)属于血红素结合单加氧酶的CYP450超家族,该家族催化各种内源性和外源性底物的氧化。Cyp1b1的表达在小梁网(TM)的发育和功能调节中起重要作用。原发性先天性青光眼(PCG)患者中已报道Cyp1b1存在突变。缺乏Cyp1b1的小鼠在TM中也表现出与先天性青光眼患者报道的类似发育缺陷。然而,Cyp1b1缺乏如何导致TM发育异常仍不清楚。在本综述中,我们将探讨Cyp1b1表达和/或其功能在前段发育中的意义。Cyp1b1缺陷(Cyp1b1(-/-))小鼠被作为PCG氧化应激诱导模型的一个有前景的模型进行讨论,其中Cyp1b1活性被揭示为氧化稳态的重要调节因子,有助于TM的发育和结构功能。这一结论提示了对有遗传高风险患PCG个体的一种可能的临床干预措施。