【摘要】 目的探讨CYP1B1基因敲除小鼠是否存在视网膜神经节细胞(RGCs)和视乳头结构的改变,以及这些改变与前房角发育之间是否存在关系。方法采用18只成年CYP1B1基因敲除小鼠作为实验对象,随机分成3组,每组6只,分别对视网膜、视乳头及前房角进行光学显微镜和透射电子显微镜观察,并用末端脱氧核苷酸转移酶介导的三磷酸脱氧尿苷缺口末端标记(TUNEL)法检测凋亡的视网膜神经细胞。以同龄C57BL/6J小鼠作对照研究。结果正常对照小鼠未发现视网膜、视乳头及前房角的异常改变。CYP1B1基因敲除小鼠中,光镜组观察发现2只眼视乳头形态结构的改变;电镜组观察发现2只眼RGCs呈现进行性的细胞浆和细胞核的浓缩;TUNEL染色组显示3只眼RGCs层和内核层出现TUNEL阳性细胞。上述7只眼均存在较严重的房角发育畸形。结论CYP1B1基因敲除小鼠部分存在RGCs的变性和视乳头结构的改变,这些改变与前房角发育畸形存在一定的相关性。更多还原

【Abstract】 ObjectiveThe epidemiological survey suggested that primary congenital glaucoma is correlated with CYP1B1 mutation.Other researcher also found the malformed development of aqueous flowing canal in CYP1B1-knockout mice.The purpose of this study was to explore whether retinal ganglion cells damage and optic papilla changes occur in the CYP1B1-knockout mice and the relationship between these alterations to anterior chamber angle development by histopathology investigation.MethodsEighteen adult CYP1B1-knockout mice were averagely assigned to 3 groups.Eighteen C57BL/6J mice were randomly divided groups at a same way as control.The retinal morphology and structure of CYP1B1-knockout mice and C57BL/6J mice,the optic papilla and the anterior chamber angle morphologies were studied by light microscope and transmission electron microscope.The apoptosis of the retinal cells was assayed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL).ResultsNo obvious morphologic changes of retina,optic papilla and dysgenesis of anterior chamber angle were found under the light microscope and transmission electron microscope in C57BL/6J mice.However,in CYP1B1-knockout mice,expanding of optic disc,edema and disruption of nerve bundles were displayed in 2 eyes under light microscope,and progressive condensation and shrinkage of the retinal ganglion cells nuclei were exhibited in other 2 eyes under the electron microscope.The apoptosis cells in the ganglion cell layer and inner nuclear layer were obviously increased in 3 eyes by TUNEL staining.The anterior chamber angle dysgenesis could be found in above 7 eyes,exhibiting the blockage of trabecular meshwork and Schlemm’s canal.ConclusionA part of CYP1B1-knockout mice appear retinal ganglion cells damage and optic papilla changes,and these alterations are positive correlated with the anterior chamber angle dysgenesis.更多还原