眼球发育相关基因与原发性闭角型青光眼的关系

Relationship between genes related to eye development and primary angle closure glaucoma

原发性闭角型青光眼(primary angle closure glaucoma,PACG)系一类复杂的多因素疾病,遗传因素在其发生发展中起重要作用.浅前房、短眼轴、厚晶状体、小角膜、远视等解剖特征是PACG发生的重要危险因素,与这些表型相关的基因成为PACG的候选基因.基质金属蛋白酶(extracellular matrix metalloprotease,MMP)基因及MMP调控基因(如HSP70、eNOS、MTHFR)、真性小眼球相关基因(MFRP、PRSS56)、眼轴及屈光度相关基因(HGF、MYOC)、与前房深度相关的基因(ABCC5)等序列变异可能与PACG的易感性有关.但这些基因的详细作用机制及生物学功能尚不明确.MMP通过影响巩膜细胞外基质的重建而影响眼球发育进而导致眼轴改变及屈光不正.膜样卷曲相关蛋白(membrane frizzled-related protein,MFRP)在睫状体上皮和视网膜色素上皮中表达,与巩膜生长、分化有关.目前候选基因法发现的这些PACG易感基因位点样本量小,在不同的种族间重复性较差.

Primary angle closure glaucoma(PACG)is a complex multifactorial disease,and heredity plays an important role in its occurrence and development.Anatomical features such as shallow anterior chamber,short eyeball,thick lens,small corneal diameter and hyperopia are important risk factors for the occurrence of PACG,so genes related to these phenotypes become candidate genes for PACG.Extracellular matrix metalloprotease(MMP)gene and MMP regulatory genes(HSP70,eNOS,MTHFR),nanophthalmos related genes(MFRP,PRSS56),axial length and diopter related genes(HGF,MYOC),and anterior chamber depth related gene(ABCC5)may be related to the susceptibility of PACG.However,the mechanisms of these genes are poorly understood.MMP affects the remodeling of the sclera extracellular matrix during eye development,resulting in changes in the ocular axis and refractive errors.Membrane frizzled-related protein(MFRP)is expressed in ciliary body epithelium and retinal pigment epithelium,which is related to scleral growth and differentiation.Up till now,there exists inconsistencies in different ethnic backgrounds of these candidate gene studies due to the small sample size.