神经生长因子蛋白及其mRNA与形觉剥夺性近视发展的关系
摘要
背景和目的
近视眼是目前全球发生率最高的屈光不正，且有不断增强的流行趋势，已经成为严重的公共卫生问题。世界卫生组织(WHO)已将近视眼的防治列为全球防盲计划之一。高度近视又称病理性近视或变性近视，约占原发近视的3％～6％。其病理机制至今不明。但形觉剥夺理论认为形觉剥夺主要通过局部视网膜机制来调控邻近巩膜的生长，视网膜含有多种神经递质，形觉剥夺可以导致神经递质水平发生改变，参与调控形觉剥夺性近视(form deprivation myopia，FDM)的形成。
神经生长因子(nerve growth factor，NGF)的发现已经有五十年的历史。其主要通过受体，TrkA和P75，兼有调控神经元和非神经元的分化增殖和维持其功能的双重作用。NGF不仅产生和表达于视网膜，维持三级神经元的塑形和功能建立，又与现已证实的多种控制FDM发生的生物物质之间相互作用，而且也产生和表达于软骨细胞，可能促进其分裂增生。Nastri G(1998)将抗鼠NGF免疫血清通过局部点眼的方式阻止了鸡近视的发展，提出了NGF可能参与近视形成的推测。但长期以来未见对其机制研究的报道。
本实验从蛋白和分子水平研究了FDM形成过程中，NGF在视网膜和巩膜细胞
郑州大学2004届硕士毕业论文
摘要
中的变化规律，以探讨NGF与FDM发生和发展的关系.
材料和方法
选用健康雄性海兰鸡雏30只，随机分为3组，每组10只。实验前对鸡进行
检影验光，排除先天性近视。于出生后第二天将右眼以半透明眼罩遮盖作为遮盖
眼，左眼开放作为对照眼。分别遮盖3天、1周和2周。最后随即选取每组6只。
去除眼罩，暗室验光，确定剥夺眼及对照眼的光状态。处死，迅速取出眼球，剪
除眼球周围软组织，用游标卡尺测量眼轴长。固定、脱水、二甲苯透明和石蜡包
埋。所有腊块连续切片，4um厚共4张，6um厚共4张。常规HE染色、免疫组织
化学染色和原位杂交染色，油镜下在视网膜的后极部取6个视野，分别计算节细
胞层和巩膜软骨层的阳性细胞百分比数及内核层每视野中阳性细胞个数，求得平
均值。
结果
(l)遮盖眼的眼轴较对照眼明显增长，随遮盖时间的延长明显增长(尸<
0.001)。眼轴的增长与负性屈光度的增加之间存在明显正相关(齐0.983)。
( 2) HE染色显示:遮盖眼巩膜的形态学变化主要集中于后极部，赤道部
变化最不明显。软骨层增厚，双极细胞增多，软骨细胞绝对数目上升，但密度下
降。遮盖眼视网膜内丛状层、内核层变薄。
(3)免疫组化染色显示:NGF蛋白主要表达于视网膜节细胞、内核层细胞、
内丛状层和巩膜软骨细胞(尤其双核细胞)，胞浆呈棕褐色颗粒状着色。形觉剥
夺使鸡遮盖眼较对照眼阳性细胞率(数)明显增加，但是随着时间的延长对照眼
和遮盖眼中阳性细胞率(数)不断显著下降。鸡遮盖眼眼轴长(y)与内核层阳
性细胞数(x、)、节细胞阳性率(xZ)和巩膜细胞阳性率(x3)与之间存在线性关
系，其多元线性回归方程为y二17.621一0.583x厂0.236x2一0.222x3。其中，遮盖眼
内核层阳性细胞数(标化回归系数=一0.583)与眼轴长之间关系最为密切。
(4)原位杂交显示:NGF mRNA主要表达于视网膜节细胞、内核层细胞、
内丛状层和巩膜软骨细胞(尤其双核细胞)，胞浆呈棕褐色颗粒状着色。形觉剥
夺使鸡遮盖眼较对照眼阳性细胞率(数)明显增加，但是随着时间的延长对照眼
和遮盖眼中阳性细胞率(数)不断显著下降。
(5)鸡遮盖眼视网膜和巩膜中表达NGF蛋白的阳性细胞数与表达
郑州大学20C.4届硕士毕业论文
摘要
NGF赦NA的阳性细胞数之间存在正相关，即形觉剥夺引起视网膜中NGF的增加，
主要来源于细胞的自分泌。其中，内核层细胞最明显(r=0 .900)，其次是巩膜
软骨细胞(r=0 .762)和节细胞(厂=0 .638)。
结论
(l)雏鸡形觉剥夺能产生明显近视，且随遮盖时间的延长近视程度不断
加深。
(2)形觉剥夺可造成雏鸡的视网膜结构发生改变，可看作是视网膜发育
的一种损伤因素。形觉剥夺性近视的形成是鸡软骨巩膜主动塑形的结果。
(3)雏鸡视网膜节细胞和内核层细胞可以自分泌的形式产生和获得神经
生长因子，促进其本身及内丛状层的功能和形态的建立。但随着年龄的增加，这
些细胞功能和形态日渐成熟，对NGF的依赖性也逐渐下降。形觉剥夺可使这种对
NGF的依赖性维持更长的时间。
(4)视网膜节细胞参与了FDM的形成。
(5)软骨细胞可以自分泌的形式产生和获得NGF以促进自身的分裂增殖。
(6)NGF参与了FDM的形成。尽管FDM形成过程中，雏鸡视网膜自分泌
NGF的绝对量增多，但对于形觉剥夺情况下视网膜功能和形态的建立又是相对不
足的。
Background and Purpose
Myopia is a leading cause of loss of vision throughout the world, and its prevalence is increasing. The World Health Organization (WHO) has already ranged it in the World Prevention of Blindness Plans. High myopia is also called as pathological myopia or degeneration myopia. Its incidence is estimated at 3~6% in the people of myopia. Its pathogenesis is holding unclear today, but form deprivation theory argues that the local retina controls the abnormal growth of the sclera leading to myopia. Many factors in the retina whose amount changes as a response of form deprivation play important roles in the development of FDM.
Nerve growth factor is discovered before more than 50 years. It exerts
effects by signaling through surface membrane receptors , trkA and P75 in the neurotissue and unneurotissue. NGF expresses and influences the shape and function of the three kinds of neuron in the retina. Nastri G (1998) had discovered that Anti-NGF serum eye drops were able to elicit a slight contraction on ocular overgrowth in chicks raised in continuous light. He suggested the NGF was possible to take part in the development of FDM.
To determine the role of nerve growth factor (NGF) in the development of FDM in the chicks, we evaluated the expressions of NGF and its mRNA in the chicken retina by immunohistochemistry and in situ hybridization. Materials and Methods
30 male hailen chicks were selected and were randomly divided into 3 groups. All right eyes underwent form deprivation with transplant goggles, and the left eyes were used as control. After the right eyes were randomly occluded for 3 , 7 , 14 days, the refractive state was respectively determined by means of streak retinascopy ( without cycloplegia ). Extracted the eyes and measured the axial length and equatorial diameter with vernier calliper, before routine fixation, dehydration, paraffin embedding, 4 and 6um paraffin sections were taken. Routine hematoxylin-eosin (HE), immunohistochemistry staining and in situ hybridization were respectively used to study the morphological changes in the retina and sclear under light microscope.
Results
(1 )Form deprivation could lead to development of myopia: the axial length had signigicant difference between the occluded eyes and the control eyes (P< 0.001). The longer the eyes were occluded, the more serious the myopia was, and there was significant difference among groups at different time. There was the linear correlation between the refractive state and the axial length in the occluded eyes (r=0.983) .
(2) HE staining showed that the occluded retina especially the inner plexus layer, became thinner and the posterior cartilaginous sclera become thicker than the control retina. There were larger number of the binuclear cells in the posterior cartilaginous sclera where the density of cells became decrease.
(3 ) Immunohistochemical staining showed that NGF positive expression was detected in the ganglion cell layer (GCL) , inner nuclear layer (INL) and sclera layer (SL), especially in the binuclear cells. The rate or amount of the positive cells in the occluded eyes was significantly higher than the control in the same group. The rate or amount of the positive cells among the occluded eyes and the control eyes significantly decreased along with the time. In the occluded eyes, there was multiple linear regression among the axial length (y), the positive rate of GCs (x3, Bi=-0.236) , the positive rate of the sclera (x2, Bi=-0.222) , and the positive amount in INL ( xh Bi=-0.583 ) . Its equation was
y=17.621-0.583xr0.236x2-0.222x3.
(4) The positive cells labelled NGF mRNA were detected in the GCL, INL and chondrocyte in the sclera. The rate or amount of the positive cells in the occluded eyes was significantly higher than the control in the same group. The rate or amount of the positive cells among the occluded eyes and the control eyes significantly decreased along with the time.
(5 ) The positive cells expressing NGF had positive correlation with these expressing NGF mRNA in the occluded e
近视眼是目前全球发生率最高的屈光不正，且有不断增强的流行趋势，已经成为严重的公共卫生问题。世界卫生组织(WHO)已将近视眼的防治列为全球防盲计划之一。高度近视又称病理性近视或变性近视，约占原发近视的3％～6％。其病理机制至今不明。但形觉剥夺理论认为形觉剥夺主要通过局部视网膜机制来调控邻近巩膜的生长，视网膜含有多种神经递质，形觉剥夺可以导致神经递质水平发生改变，参与调控形觉剥夺性近视(form deprivation myopia，FDM)的形成。
神经生长因子(nerve growth factor，NGF)的发现已经有五十年的历史。其主要通过受体，TrkA和P75，兼有调控神经元和非神经元的分化增殖和维持其功能的双重作用。NGF不仅产生和表达于视网膜，维持三级神经元的塑形和功能建立，又与现已证实的多种控制FDM发生的生物物质之间相互作用，而且也产生和表达于软骨细胞，可能促进其分裂增生。Nastri G(1998)将抗鼠NGF免疫血清通过局部点眼的方式阻止了鸡近视的发展，提出了NGF可能参与近视形成的推测。但长期以来未见对其机制研究的报道。
本实验从蛋白和分子水平研究了FDM形成过程中，NGF在视网膜和巩膜细胞
郑州大学2004届硕士毕业论文
摘要
中的变化规律，以探讨NGF与FDM发生和发展的关系.
材料和方法
选用健康雄性海兰鸡雏30只，随机分为3组，每组10只。实验前对鸡进行
检影验光，排除先天性近视。于出生后第二天将右眼以半透明眼罩遮盖作为遮盖
眼，左眼开放作为对照眼。分别遮盖3天、1周和2周。最后随即选取每组6只。
去除眼罩，暗室验光，确定剥夺眼及对照眼的光状态。处死，迅速取出眼球，剪
除眼球周围软组织，用游标卡尺测量眼轴长。固定、脱水、二甲苯透明和石蜡包
埋。所有腊块连续切片，4um厚共4张，6um厚共4张。常规HE染色、免疫组织
化学染色和原位杂交染色，油镜下在视网膜的后极部取6个视野，分别计算节细
胞层和巩膜软骨层的阳性细胞百分比数及内核层每视野中阳性细胞个数，求得平
均值。
结果
(l)遮盖眼的眼轴较对照眼明显增长，随遮盖时间的延长明显增长(尸<
0.001)。眼轴的增长与负性屈光度的增加之间存在明显正相关(齐0.983)。
( 2) HE染色显示:遮盖眼巩膜的形态学变化主要集中于后极部，赤道部
变化最不明显。软骨层增厚，双极细胞增多，软骨细胞绝对数目上升，但密度下
降。遮盖眼视网膜内丛状层、内核层变薄。
(3)免疫组化染色显示:NGF蛋白主要表达于视网膜节细胞、内核层细胞、
内丛状层和巩膜软骨细胞(尤其双核细胞)，胞浆呈棕褐色颗粒状着色。形觉剥
夺使鸡遮盖眼较对照眼阳性细胞率(数)明显增加，但是随着时间的延长对照眼
和遮盖眼中阳性细胞率(数)不断显著下降。鸡遮盖眼眼轴长(y)与内核层阳
性细胞数(x、)、节细胞阳性率(xZ)和巩膜细胞阳性率(x3)与之间存在线性关
系，其多元线性回归方程为y二17.621一0.583x厂0.236x2一0.222x3。其中，遮盖眼
内核层阳性细胞数(标化回归系数=一0.583)与眼轴长之间关系最为密切。
(4)原位杂交显示:NGF mRNA主要表达于视网膜节细胞、内核层细胞、
内丛状层和巩膜软骨细胞(尤其双核细胞)，胞浆呈棕褐色颗粒状着色。形觉剥
夺使鸡遮盖眼较对照眼阳性细胞率(数)明显增加，但是随着时间的延长对照眼
和遮盖眼中阳性细胞率(数)不断显著下降。
(5)鸡遮盖眼视网膜和巩膜中表达NGF蛋白的阳性细胞数与表达
郑州大学20C.4届硕士毕业论文
摘要
NGF赦NA的阳性细胞数之间存在正相关，即形觉剥夺引起视网膜中NGF的增加，
主要来源于细胞的自分泌。其中，内核层细胞最明显(r=0 .900)，其次是巩膜
软骨细胞(r=0 .762)和节细胞(厂=0 .638)。
结论
(l)雏鸡形觉剥夺能产生明显近视，且随遮盖时间的延长近视程度不断
加深。
(2)形觉剥夺可造成雏鸡的视网膜结构发生改变，可看作是视网膜发育
的一种损伤因素。形觉剥夺性近视的形成是鸡软骨巩膜主动塑形的结果。
(3)雏鸡视网膜节细胞和内核层细胞可以自分泌的形式产生和获得神经
生长因子，促进其本身及内丛状层的功能和形态的建立。但随着年龄的增加，这
些细胞功能和形态日渐成熟，对NGF的依赖性也逐渐下降。形觉剥夺可使这种对
NGF的依赖性维持更长的时间。
(4)视网膜节细胞参与了FDM的形成。
(5)软骨细胞可以自分泌的形式产生和获得NGF以促进自身的分裂增殖。
(6)NGF参与了FDM的形成。尽管FDM形成过程中，雏鸡视网膜自分泌
NGF的绝对量增多，但对于形觉剥夺情况下视网膜功能和形态的建立又是相对不
足的。
Background and Purpose
Myopia is a leading cause of loss of vision throughout the world, and its prevalence is increasing. The World Health Organization (WHO) has already ranged it in the World Prevention of Blindness Plans. High myopia is also called as pathological myopia or degeneration myopia. Its incidence is estimated at 3~6% in the people of myopia. Its pathogenesis is holding unclear today, but form deprivation theory argues that the local retina controls the abnormal growth of the sclera leading to myopia. Many factors in the retina whose amount changes as a response of form deprivation play important roles in the development of FDM.
Nerve growth factor is discovered before more than 50 years. It exerts
effects by signaling through surface membrane receptors , trkA and P75 in the neurotissue and unneurotissue. NGF expresses and influences the shape and function of the three kinds of neuron in the retina. Nastri G (1998) had discovered that Anti-NGF serum eye drops were able to elicit a slight contraction on ocular overgrowth in chicks raised in continuous light. He suggested the NGF was possible to take part in the development of FDM.
To determine the role of nerve growth factor (NGF) in the development of FDM in the chicks, we evaluated the expressions of NGF and its mRNA in the chicken retina by immunohistochemistry and in situ hybridization. Materials and Methods
30 male hailen chicks were selected and were randomly divided into 3 groups. All right eyes underwent form deprivation with transplant goggles, and the left eyes were used as control. After the right eyes were randomly occluded for 3 , 7 , 14 days, the refractive state was respectively determined by means of streak retinascopy ( without cycloplegia ). Extracted the eyes and measured the axial length and equatorial diameter with vernier calliper, before routine fixation, dehydration, paraffin embedding, 4 and 6um paraffin sections were taken. Routine hematoxylin-eosin (HE), immunohistochemistry staining and in situ hybridization were respectively used to study the morphological changes in the retina and sclear under light microscope.
Results
(1 )Form deprivation could lead to development of myopia: the axial length had signigicant difference between the occluded eyes and the control eyes (P< 0.001). The longer the eyes were occluded, the more serious the myopia was, and there was significant difference among groups at different time. There was the linear correlation between the refractive state and the axial length in the occluded eyes (r=0.983) .
(2) HE staining showed that the occluded retina especially the inner plexus layer, became thinner and the posterior cartilaginous sclera become thicker than the control retina. There were larger number of the binuclear cells in the posterior cartilaginous sclera where the density of cells became decrease.
(3 ) Immunohistochemical staining showed that NGF positive expression was detected in the ganglion cell layer (GCL) , inner nuclear layer (INL) and sclera layer (SL), especially in the binuclear cells. The rate or amount of the positive cells in the occluded eyes was significantly higher than the control in the same group. The rate or amount of the positive cells among the occluded eyes and the control eyes significantly decreased along with the time. In the occluded eyes, there was multiple linear regression among the axial length (y), the positive rate of GCs (x3, Bi=-0.236) , the positive rate of the sclera (x2, Bi=-0.222) , and the positive amount in INL ( xh Bi=-0.583 ) . Its equation was
y=17.621-0.583xr0.236x2-0.222x3.
(4) The positive cells labelled NGF mRNA were detected in the GCL, INL and chondrocyte in the sclera. The rate or amount of the positive cells in the occluded eyes was significantly higher than the control in the same group. The rate or amount of the positive cells among the occluded eyes and the control eyes significantly decreased along with the time.
(5 ) The positive cells expressing NGF had positive correlation with these expressing NGF mRNA in the occluded e
引文
[1]瞿佳．坚持防治近视眼研究的正确方向．中华眼科杂志．2003，39(6)：321
[2]汪芳润，编著．近视眼．上海：上海医科大学出版社．1996，13-20
[3]Wiesel YN, Ravio la E. Myopia and eye enlargement after neonatal lid fusion in monkeys. Nature. 1977, 286:266-268
[4]朱玉广，刘双珍．视网膜神经递质系统在形觉剥夺性近视中的调控作用．眼科新进展．2003，23(2)：138
[5]孙声桃，郭希让．神经生长因子及其受体与视神经视网膜疾病的研究进展．眼科新进展．2002，22(1)：57
[6]蒋永祥，郭希让．神经生长因子细胞保护作用的应用研究进展．眼科研究．2002，20(1)：83
[7]Sofroniew MV, Howe CL, Mobley Wc. Nerve growth factor signaling, neuroprotection, and neural repair. Annu. Rev. Neurosci. 2001,24:1217
[8]Nastri G, Benusiglio E, Sellitti L, et al. Does anti-NGF inhibit deprivative myopia onset? InterNet J Ophthalmol. 1998, 3:30
[9]Wildsoet F, Wallman J. Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks. Vision Res. 1995, 35:1175-1194
[10]S. S. Guo, J.G. Sivak, M. G. Callender, et al. Effects of continuous light on experimental refractive errors in chicks. Ophthal. Physiol. Opt.1996, 16(6): 486-490
[11]Wiesel T.N, Raviola E. Increase in axial length of the macaque monkey eye after corneal opacification. Investigative Opthalmology & Visual Science. 1979, 18:1232-1236
[12]Karla Zadnik, Donald O. Mutti. How applicabke are animal myopia models to human juvenile onset myopia? Vision Res. 1995, 35(9): 1283-1288
[13]胡磊，李军，汪芳润．实验性近视研究进展．中国斜视与小儿眼科杂志，1996，4：92
[14]Edwards MH. Animal models of myopia. Acta Ophthalmol Scand. 1996,74:213
[15]C. Wiesmann. Nerve growth factor: structure and function. CMLS,Cell. Mol. Life Sci. 2001, 58:748-759
[16]Wallmann J. Nature and nurture of myopia. Nature. 1994,371:201-202
[17]Rada JA, Matthews AL. Visual deprivation upregulates extracellular matrix synthesis by chick sclera chondrocytes. Invest Ophthalmal Vis Sci. 1994, 35(5): 2436-2447
[18]胡文政，褚仁远．近视眼巩膜的变化及其发生机制．眼视光学杂志．2001，3(1)：57
[19]席晓琼，褚仁远，陈荣家．实验性近视眼组织病理及超微结构观察．眼科新进展．2001，21(5)：329-331
[20]Liang H, Crewther DP. A role for photoreceptor outer segments in the induction of deprivation myopia. Vision Res. 1995, 35(9): 1217-1225
[21]刘扬，易明望，管志华，等．实验性近视眼视网膜机制的研究进展．眼视光学杂志．2001，3(2)：123
[22]张伟，赵堪兴．视觉形成的神经机制．眼科研究．2002，20(5)：472
[23]朱玉广，刘双珍．视网膜神经递质系统在形觉剥夺性近视中的调控作用．眼科新进展．2003，23(2)：138
[24]杨雄里．脑的奥秘．第一版．长沙：湖南科学技术出版社．1995，83
[25]Sofroniew MV, Howe CL, Mobley Wc. Nerve growth factor signaling, neuroprotection, and neural repair. Annu. Rev. Neurosci. 2001,24:1217
[26]Harada T, Harada C, et al. Microglia-muller glia cell interactions contral neurotrophic factor production during light induced retinal
degeneration. J Neurosci, 2002, 22(21):9228
[27]Troilo. D., Gottlieb, Wallman. Visual deprivation causes myopia in chicks with optic nerve section. Curt. Eye Rese. 1987, 6:993-999
[28]C.F. Wildsoet, K.L. Schmid. Optical correction of form deprivation myopia inhibits refractive recovery in chick eyes with intact or sectioned optic nerves. Vision Res. 2000, 40: 3273-3282
[29]Domenici L, Berardi N, et al. Nerv growth factor prevents the amblyopic effects of monocular deprivation. Proc Natl Acad Sci SA. 1991(88): 8811-8815
[30]屠一帆，黄倩，赵新峰．多巴胺在形觉剥夺性近视眼中的作用．眼视光学杂志．2002，4(3)：190
[31]程序，徐亮，白凤阁．鸡形觉剥夺性近视眼视网膜电图改变．眼科，2000，9(3)：174
[32]Iannone F, De Bari C, Dell'Accio F, et al. Increased expression of nerve growth factor (NGF) and high affinity NGF receptor(p140 TrkA) in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2002,41(12):1413
[33]Vecino E, Caminos E, Ugarte M, et al. Immunohistochemical distribution of neurotrophins and their receptors in the rat retina and the effects of ischemia and reperfusion. Gen Pharmacol.1998(3):305-314
[2]汪芳润，编著．近视眼．上海：上海医科大学出版社．1996，13-20
[3]Wiesel YN, Ravio la E. Myopia and eye enlargement after neonatal lid fusion in monkeys. Nature. 1977, 286:266-268
[4]朱玉广，刘双珍．视网膜神经递质系统在形觉剥夺性近视中的调控作用．眼科新进展．2003，23(2)：138
[5]孙声桃，郭希让．神经生长因子及其受体与视神经视网膜疾病的研究进展．眼科新进展．2002，22(1)：57
[6]蒋永祥，郭希让．神经生长因子细胞保护作用的应用研究进展．眼科研究．2002，20(1)：83
[7]Sofroniew MV, Howe CL, Mobley Wc. Nerve growth factor signaling, neuroprotection, and neural repair. Annu. Rev. Neurosci. 2001,24:1217
[8]Nastri G, Benusiglio E, Sellitti L, et al. Does anti-NGF inhibit deprivative myopia onset? InterNet J Ophthalmol. 1998, 3:30
[9]Wildsoet F, Wallman J. Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks. Vision Res. 1995, 35:1175-1194
[10]S. S. Guo, J.G. Sivak, M. G. Callender, et al. Effects of continuous light on experimental refractive errors in chicks. Ophthal. Physiol. Opt.1996, 16(6): 486-490
[11]Wiesel T.N, Raviola E. Increase in axial length of the macaque monkey eye after corneal opacification. Investigative Opthalmology & Visual Science. 1979, 18:1232-1236
[12]Karla Zadnik, Donald O. Mutti. How applicabke are animal myopia models to human juvenile onset myopia? Vision Res. 1995, 35(9): 1283-1288
[13]胡磊，李军，汪芳润．实验性近视研究进展．中国斜视与小儿眼科杂志，1996，4：92
[14]Edwards MH. Animal models of myopia. Acta Ophthalmol Scand. 1996,74:213
[15]C. Wiesmann. Nerve growth factor: structure and function. CMLS,Cell. Mol. Life Sci. 2001, 58:748-759
[16]Wallmann J. Nature and nurture of myopia. Nature. 1994,371:201-202
[17]Rada JA, Matthews AL. Visual deprivation upregulates extracellular matrix synthesis by chick sclera chondrocytes. Invest Ophthalmal Vis Sci. 1994, 35(5): 2436-2447
[18]胡文政，褚仁远．近视眼巩膜的变化及其发生机制．眼视光学杂志．2001，3(1)：57
[19]席晓琼，褚仁远，陈荣家．实验性近视眼组织病理及超微结构观察．眼科新进展．2001，21(5)：329-331
[20]Liang H, Crewther DP. A role for photoreceptor outer segments in the induction of deprivation myopia. Vision Res. 1995, 35(9): 1217-1225
[21]刘扬，易明望，管志华，等．实验性近视眼视网膜机制的研究进展．眼视光学杂志．2001，3(2)：123
[22]张伟，赵堪兴．视觉形成的神经机制．眼科研究．2002，20(5)：472
[23]朱玉广，刘双珍．视网膜神经递质系统在形觉剥夺性近视中的调控作用．眼科新进展．2003，23(2)：138
[24]杨雄里．脑的奥秘．第一版．长沙：湖南科学技术出版社．1995，83
[25]Sofroniew MV, Howe CL, Mobley Wc. Nerve growth factor signaling, neuroprotection, and neural repair. Annu. Rev. Neurosci. 2001,24:1217
[26]Harada T, Harada C, et al. Microglia-muller glia cell interactions contral neurotrophic factor production during light induced retinal
degeneration. J Neurosci, 2002, 22(21):9228
[27]Troilo. D., Gottlieb, Wallman. Visual deprivation causes myopia in chicks with optic nerve section. Curt. Eye Rese. 1987, 6:993-999
[28]C.F. Wildsoet, K.L. Schmid. Optical correction of form deprivation myopia inhibits refractive recovery in chick eyes with intact or sectioned optic nerves. Vision Res. 2000, 40: 3273-3282
[29]Domenici L, Berardi N, et al. Nerv growth factor prevents the amblyopic effects of monocular deprivation. Proc Natl Acad Sci SA. 1991(88): 8811-8815
[30]屠一帆，黄倩，赵新峰．多巴胺在形觉剥夺性近视眼中的作用．眼视光学杂志．2002，4(3)：190
[31]程序，徐亮，白凤阁．鸡形觉剥夺性近视眼视网膜电图改变．眼科，2000，9(3)：174
[32]Iannone F, De Bari C, Dell'Accio F, et al. Increased expression of nerve growth factor (NGF) and high affinity NGF receptor(p140 TrkA) in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2002,41(12):1413
[33]Vecino E, Caminos E, Ugarte M, et al. Immunohistochemical distribution of neurotrophins and their receptors in the rat retina and the effects of ischemia and reperfusion. Gen Pharmacol.1998(3):305-314