大鼠视网膜在胚胎及发育过程中的形态学改变及HIF-1α的表达
摘要
目的观察大鼠视网膜胚胎发育过程中神经细胞分化、组织结构的改变及低氧诱导因子-1α(hypoxia inducible facter 1α，HIF-1α)的时空表达，探讨HIF 1α在视网膜发生和发育过程中的作用。
方法对胚胎10天～20天(E10～E20)、生后(P0)至成年(12个月龄)大鼠视网膜进行光镜和电镜观察；用免疫组织化学方法、PCR方法检测视网膜HIF-1α蛋白及HIF-1αmRNA的表达。
结果大鼠视网膜发育起自胚胎10天(E10)，胚鼠视杯形成，分内、外两层；胚胎14天(E14)，外层色素上皮细胞呈单层排列，神经上皮层逐渐增厚；胚胎16天(E16)，神经上皮层分为两部分：外成神经细胞层和内成神经细胞层；胚胎18天(E18)，出现染色浅淡的chievitz层；E20时，内网层形成，神经节细胞开始分化。生后1天(P1)，视网膜组织分为色素上皮细胞层、神经母细胞层和神经节细胞层；生后7天(P7)内外核层出现，出生后15天(P15)视网膜出现10层结构。低氧诱导因子-1在大鼠视网膜表达为胚胎期高表达、生后发育期表达较弱、成年期微弱表达，三期之间的差异有统计学意义(P＜0.05)。
结论大鼠视网膜发生起始于胚胎第10天。胚胎14天，外层色素上皮细胞呈单层排列。神经上皮层随胎龄增加逐渐发育分化。新生大鼠视网膜组织发育不完善，至出生后15天视网膜各层的分化基本完成；HIF-1α在大鼠胚胎期视网膜的高表达说明在胚胎期，尤其是胚胎早期视网膜的发育存在低氧环境，HIF-1α可能参与了大鼠视网膜的胚胎发育过程。
Objective To investigate the differentiation of nerve cells、alternation of tissue andspace-time expression of hypoxia inducible factor 1(HIF-1) during embryonicdevelopment of rat retina, and explore the role of HIF 1 in retina development withinthis time.
Method Rat retina of embryo 10 days-20 days (E10-E20)、postnatal (PO) and adult(12 months) was examined by light and electron microscopes; Different expression of HIF-1αprotein and HIF-1αmRNA was examined by immunohistochemical and RT-PCR methods.
Result The development of rat retina began in 10th day of embryo (E10), andoptic cup was formed including inner and outer layer; in 14th day of embryo (E14), the pigmentepithelium cell of outer layer was monolayer arranged,and the neural epithelium became thinckinggradually.; in 16th day of embryo(E16), the neural epithelium became two parts: inner and outerneural layers; in 18th day of embryo(E18), chievitz layer with light staining appeared; in 20th dayof embryo(E20), inner plexiform layer was formed and gangliocyte became differentiation. in thefirst day of postnatal (P1), retina was divided into pigment epithelium layer、neuroblast layer andgangliocyte layer; in 7th day of postnatal (P7), inner and outer nuclear layers emerged, and in15th day of postnatal (P15) retina formed the structure of 10 layers. HIF-1αin rat retinaexpressed highly in embryo、lower postnatal and lowest in adult,
Conclusion The development of rat retina begin at 10th day of embryo. In 14thday of embryo, outer pigment epithelium cell became monolayer, and neuralepithelium was differentiating gradually, newly born rat retina developes insufficiently,and till postnatal 15th day, the differentiation of retinal lays primarily completes. The highlyexpression of HIF-1αof embryo promote in this period hypoxia circumstance existespecially in earlier embryo. So HIF-1αmight participate the process of embryo developmentof rat retina.
方法对胚胎10天～20天(E10～E20)、生后(P0)至成年(12个月龄)大鼠视网膜进行光镜和电镜观察；用免疫组织化学方法、PCR方法检测视网膜HIF-1α蛋白及HIF-1αmRNA的表达。
结果大鼠视网膜发育起自胚胎10天(E10)，胚鼠视杯形成，分内、外两层；胚胎14天(E14)，外层色素上皮细胞呈单层排列，神经上皮层逐渐增厚；胚胎16天(E16)，神经上皮层分为两部分：外成神经细胞层和内成神经细胞层；胚胎18天(E18)，出现染色浅淡的chievitz层；E20时，内网层形成，神经节细胞开始分化。生后1天(P1)，视网膜组织分为色素上皮细胞层、神经母细胞层和神经节细胞层；生后7天(P7)内外核层出现，出生后15天(P15)视网膜出现10层结构。低氧诱导因子-1在大鼠视网膜表达为胚胎期高表达、生后发育期表达较弱、成年期微弱表达，三期之间的差异有统计学意义(P＜0.05)。
结论大鼠视网膜发生起始于胚胎第10天。胚胎14天，外层色素上皮细胞呈单层排列。神经上皮层随胎龄增加逐渐发育分化。新生大鼠视网膜组织发育不完善，至出生后15天视网膜各层的分化基本完成；HIF-1α在大鼠胚胎期视网膜的高表达说明在胚胎期，尤其是胚胎早期视网膜的发育存在低氧环境，HIF-1α可能参与了大鼠视网膜的胚胎发育过程。
Objective To investigate the differentiation of nerve cells、alternation of tissue andspace-time expression of hypoxia inducible factor 1(HIF-1) during embryonicdevelopment of rat retina, and explore the role of HIF 1 in retina development withinthis time.
Method Rat retina of embryo 10 days-20 days (E10-E20)、postnatal (PO) and adult(12 months) was examined by light and electron microscopes; Different expression of HIF-1αprotein and HIF-1αmRNA was examined by immunohistochemical and RT-PCR methods.
Result The development of rat retina began in 10th day of embryo (E10), andoptic cup was formed including inner and outer layer; in 14th day of embryo (E14), the pigmentepithelium cell of outer layer was monolayer arranged,and the neural epithelium became thinckinggradually.; in 16th day of embryo(E16), the neural epithelium became two parts: inner and outerneural layers; in 18th day of embryo(E18), chievitz layer with light staining appeared; in 20th dayof embryo(E20), inner plexiform layer was formed and gangliocyte became differentiation. in thefirst day of postnatal (P1), retina was divided into pigment epithelium layer、neuroblast layer andgangliocyte layer; in 7th day of postnatal (P7), inner and outer nuclear layers emerged, and in15th day of postnatal (P15) retina formed the structure of 10 layers. HIF-1αin rat retinaexpressed highly in embryo、lower postnatal and lowest in adult,
Conclusion The development of rat retina begin at 10th day of embryo. In 14thday of embryo, outer pigment epithelium cell became monolayer, and neuralepithelium was differentiating gradually, newly born rat retina developes insufficiently,and till postnatal 15th day, the differentiation of retinal lays primarily completes. The highlyexpression of HIF-1αof embryo promote in this period hypoxia circumstance existespecially in earlier embryo. So HIF-1αmight participate the process of embryo developmentof rat retina.
引文
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[2] Cepko CL, Austin CP, Yang XJ. Cell fate determination in the vertebrate retina. Proc Natl Acad Sci. USA, 1996,93 (2) : 589-595
[3] Marquardt T, Gruss P. Generating neuronal diversity in the retina : one for nearly all. Trends Neurosci, 2002,25(1) : 32-38
[4] 吴继红，易苗英，黄倩．四种中间丝蛋白在大鼠视网膜发育过程中表达的时间顺序和结构特征．中华眼科杂志，2004，40(11)：765-769．
[5] 李艳，佘振珏，俞彰，等．胚胎大鼠视网膜超微结构与Nestin表达的增龄变化．中国组织化学与细胞化学杂志，2004，13(2)：138-141
[6] Reese BE, Collo RJ..Neurogenesis in the retinal ganglionce cell layer of the rat. Neuroscience, 1992,46:419.
[7] Bodenant C, Leroux P ,Gonzalez BJ,et al. Transient expression of somatostatin receptors in the rat visual system during development. Neuroscience, 1992,46:419.
[8] Lake N. Taurine and GABA in the rat retina during postnatal devel opment. Vis Neurosci,1994,11:253-260.
[9] Casini G, Molnar M, Brecha NC. Vasoactive intestinal polypeptide/peptide histidine isoleucine messenger RNA in the rat retina: adult distribution and developmental expression. Neuroscience,1994,58:657-667.
[10] 彭清，刘舒娅，任佩贤．不同日龄新生小鼠视网膜组织学观察．中华眼底病杂志，1999，第15(3)174-176
[11] 刘斌，高英茂主编．人体胚胎学人民卫生出版社1996年1月，第1版471-484
[12] 葛坚主编．眼科学，人民卫生出版社2005年8月，第1版10．20
[13] Semenza GL. HIF1:mediator of physiological and pathophysiological response to hypoxia[J].Appl Physiol, 2000,88(4):1474-1480
[14] Zagzag D, Zhong H, Scalzitti JM, et al. Expression of hypoxia inducible factorlalph in brain tumors:association with angiogenesis, invasion and progression [J]. Cancer, 2000,88(11):2606-2618
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