结晶样视网膜色素变性研究进展

Research progress in Bietti crystalline corneoretinal dystrophy

结晶样视网膜变性（BCD）是一种常染色体隐性遗传的进展性视网膜变性疾病，其主要的临床特征为闪亮的黄白色结晶沉积于视网膜后极部，并伴有进展性视网膜色素上皮（RPE）细胞、脉络膜毛细血管及光感受器细胞的萎缩。BCD主要的致病基因为CYP4V2。目前国内外关于BCD患者的基因研究中已发现多个基因突变位点。CYP4V2基因是细胞色素氧化酶P450家族的成员，参与多不饱和脂肪酸的ω-羟化过程。CYP4V2蛋白主要分布于RPE细胞，以二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）为特异性催化底物，在眼组织的脂质循环过程中发挥重要作用，CYP4V2基因的突变可扰乱内源性脂肪酸或类固醇的合成分解途径。目前，BCD的治疗主要参考视网膜色素变性（RP）的治疗方法，而突变位点的研究为未来的基因治疗提供了可能。了解BCD的分子遗传机制及发病的病理生理过程，将对未来BCD的诊断与潜在的基因治疗有重要意义。本文从BCD的分子遗传学机制、CYP4V2蛋白的体内表达和在脂质代谢中的作用以及BCD的治疗等方面对BCD的研究进展进行综述。

Bietti crystalline corneoretinal dystrophy （BCD） is an autosomal recessive retinal degenerative disease characterized by crystalline deposits in the retina, followed by progressive atrophy of retinal pigment epithelium （RPE）, choriocapillaris and photoreceptors.CYP4V2 has been identified as causative gene for BCD.At present, multiple gene mutation sites have been found in BCD patients.CYP4V2 gene belongs to cytochrome P450, it participates in the ω-hydroxylase activity of polyunsaturated fatty acids （PUFAs）. CYP4V2 proteins are mainly distributed in the RPE, docosahexaenoic acid （DHA） and eicosapentaenoic acid （EPA） as specific catalytic substrates, and play an important role in ocular physiological lipid recycling system.CYP4V2 gene mutations can disrupt the endogenous fatty acids or steroid synthesis and decomposition approach.The treatment of BCD always refers to retinitis pigmentosa （RP）, and the study of mutation sites have provided the possibility for future gene therapy.Understanding the mechanism of molecular genetics and the pathophysiology of disease will be useful for the genetic diagnosis of BCD and potential development of genetic therapy in the future.This article reviewed the molecular genetic mechanism of BCD, in vivo expression and role of CYP4V2 in lipid metabolism and the treatment of BCD.