左旋多巴甲酯对斜视性弱视猫模型的作用
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摘要
目的:弱视是影响儿童视力的主要疾病之一,不及时治疗可以导致终身视力低下,其发病机理尚在探索中。90年代起,国内外学者对药物治疗弱视进行了许多临床性的研究,目前临床上多采用左旋多巴治疗,取得了一定效果。然而,左旋多巴存在副作用多、耐受性差、效果不稳定等缺点。本实验组经过对左旋多巴进行结构改造得到左旋多巴甲酯(LDME)。本研究的目的是观察LDME对斜视性弱视猫模型的治疗作用,评价其治疗弱视的主要药效学作用,探讨LDME的作用机理。
     方法:正常幼猫30只随机分成6组:左旋多巴甲酯低剂量、中剂量和高剂量组、模型对照组、阳性对照组及正常对照组,每组5只,于4周龄时行眼外直肌切除术造成人工斜视(正常对照组除外),经图形视觉诱发电位(P-VEP)确定形成弱视后,灌胃给与左旋多巴甲酯20mg/kg,40mg/kg, 80mg/kg,阳性对照组给与左旋多巴40mg/kg,正常对照组及模型组均给与等量生理盐水。每天一次,连续30天。
     ①采用图形视觉诱发电位(PVEP)研究左旋多巴甲酯对各组猫视皮层机能的影响;②应用HE尼氏染色、Nissl染色和透射电镜观察左旋多巴甲酯各组猫视皮层17区形态学的改变;③应用原位杂交技术检测视皮质17区c-fos mRNA的表达情况;④应用免疫组化技术检测视皮质17区c-fos蛋白的表达情况;⑤应用免疫组化检测视皮质17区神经生长因子(NGF)的表达情况;⑥用免疫组织化学技术检测视皮质17区NOS阳性细胞的密度。
     结果:
     ⑴斜视性弱视部分的视觉电生理研究
     模型对照组(MC)主要以波幅降低及P100潜时延长为特点,MC组潜时延长,潜时较对侧眼及正常对照组双眼的潜时明显延长,差异有显著性(P<0.05);模型对照组每只猫的弱视视觉诱发电位图形P100波幅值与同自身的正常眼及正常组同侧眼比较,P100波幅值变小,差异具有统计学意义(P<0.01)。治疗后各组与模型对照组比较,潜时均有不同程度缩短,以高剂量组最为显著,差异有统计学意义(p<0.01)。经用药物治疗后弱视眼振幅升高,以高剂量组最为显著,与正常对照组比较,无统计学差异(p>0.05)。表明左旋多巴甲酯能明显地改善斜视性弱视猫模型弱视眼的传导和感觉功能。
     ⑵斜视性弱视部分的形态学研究结果
     模型组(MC)17区视皮层的神经元表现为功能减退,高剂量组、中剂量组、低剂量组及阳性对照组的神经元处于恢复状态,高剂量组的恢复优于阳性对照组、中剂量组、低剂量组。颗粒内层、颗粒外层依次恢复。
     ⑶LDME对视皮质17区c-fos mRNA表达的影响
     正常对照组猫视皮层c-fos mRNA阳性细胞分布广泛,表达活跃。杂交细胞在各层间的分布情况为:Ⅱ/Ⅲ、Ⅴ/Ⅵ层密度较高,Ⅳ层密度最低。与正常对照组相比较,模型对照组弱视猫视皮层c-fos mRNA杂交细胞在各层均减少,差异有显著性(P<0.01)。与模型对照组相比,治疗组(包括PC、LDMEL、LDMEM、LDMEH)c-fos mRNA杂交细胞在视皮质Ⅱ/Ⅲ、Ⅳ、Ⅴ/Ⅵ层均有增加,除在Ⅳ外,其余各组差异有显著性(P <0.05或P<0.01),而其中以LDMEH组最为明显(P<0.01)。
     ⑷LDME对视皮质17区Fos蛋白表达的影响
     正常对照组猫视皮质17区全层均见到胞核呈深褐色的阳性细胞,NC猫视皮质17区全层均见高水平的Fos蛋白表达,尤以Ⅱ、Ⅲ、及Ⅵ层密度为高,Ⅳ及Ⅴ层较低。模型对照组猫视皮质全层均可见到阳性细胞,层与层之间的分布模式和正常对照组相似,但各层阳性细胞密度明显降低,差异有统计学意义(P<0.01)。治疗组(包括阳性对照组、左旋多巴甲酯高、中、低剂量组)的阳性细胞的分布基本上都在Ⅱ、Ⅲ、Ⅴ及Ⅵ层,但治疗组的密度高于模型对照组,差异有显著且有统计学意义(P<0.05)。左旋多巴甲酯治疗组与阳性对照组相比较,左旋多巴甲酯治疗组各层阳性细胞分布密度均比阳性对照组高,在一些层上具有统计学意义。
     ⑸LDME对视皮质17区神经生长因子(NGF)表达的影响
     模型对照组弱视猫VC17区NGF表达特性发生改变,与正常对照组比较,模型对照组内源性NGF免疫阳性细胞数量在各层均减少,两者有显著性差异(p<0.01);通过给与盐酸左旋多巴甲酯治疗后, NGF表达增加,治疗组(包括阳性对照组、左旋多巴甲酯高、中、低剂量组)与模型对照组比较,内源性NGF免疫阳性细胞数量在各层均增加,除LDMEL在Ⅲ、Ⅴ、Ⅵ外,其余差异均有统计学意义(p<0.01或p<0.05);左旋多巴甲酯组与阳性对照组相比较,NGF免疫阳性细胞数量在各层呈上升趋势,且LDMEH在Ⅲ、Ⅵ与阳性对照组相比较差异有统计学意义(p<0.01或p<0.05)。LDMEH与正常对照组比较,NGF免疫阳性细胞数量在各层均少于正常组,但两者比较未见有统计学差异(p>0.05)
     ⑹LDME对视皮质17区NOS表达的影响
     正常对照组阳性细胞主要分布于灰质的Ⅱ、Ⅲ、Ⅳ、Ⅴ、Ⅵ层和白质中,在Ⅱ/Ⅲ层最多,Ⅴ/Ⅵ层其次,Ⅳ层最少。模型对照组视皮层17区各层NOS阳性细胞的分布模式与正常对照组相似,但各层内及层间NOS阳性纤维明显减少,模型对照组视皮层17区各层NOS阳性细胞密度均显著下降(P<0.05),其中Ⅱ/Ⅲ层及Ⅴ/Ⅵ层NOS阳性细胞密度与正常组对应层次的阳性细胞密度差别具有高度统计意义(P<0.01)。用药后治疗组(包括阳性对照组、左旋多巴甲酯高中低剂量组)各层均有恢复,以LDMEH最为明显。
     结论:
     ⑴左旋多巴甲酯缩短斜视性弱视猫弱视眼P100波峰潜时及提高P100波幅值,具有改善斜视性弱视猫弱视眼的传导和感觉功能的作用。
     ⑵左旋多巴甲酯对斜视性弱视猫神经元的损伤有较好的治疗效果,高剂量效果最好,能加快复制、转录过程,促进蛋白质的合成,使受损的神经元形态恢复并且能促进胞体突起的形成,促使突触之间的联系增多。
     ⑶左旋多巴甲酯能促进斜视性弱视猫视皮质17区c-fos mRNA的表达;
     ⑷左旋多巴甲酯能促进斜视性弱视猫视皮质17区Fos蛋白的表达。
     ⑸左旋多巴甲酯能增加斜视性弱视猫视皮质17区神经生长因子(NGF)合成与释放。NGF表达增加与PVEP的改变相吻合,证明左旋多巴甲酯能使斜视性弱视猫弱视眼的视功能得到一定的改善。NGF作为一种细胞功能的调控因子,可能在视觉系统发育的可塑性方面发挥重要作用。左旋多巴甲酯通过NGF的作用,参与视觉系统发育的可塑性。
     ⑹左旋多巴甲酯能在一定程度上提高斜视性弱视猫视皮质17区一氧化氮的水平。
     ⑺左旋多巴甲酯斜视性弱视猫有治疗作用,其治疗作用可能与左旋多巴甲酯促进斜视性弱视猫视皮质17区c-fos mRNA、Fos蛋白的表达、增加神经生长因子(NGF)合成与释放及提高斜视性弱视猫视皮质17区一氧化氮的水平有关。
Objective: Amblyopia is one of the major diseases affecting children vission, it can lead to lifelong poor vision if not treated in time. The formation of amblyopia involves a variety of factors, and its pathogenesis is still under exploration. From the 90s onwards, domestic and foreign scholars have done many clinical studies on the use of drug treatment of amblyopia. At present, clinically L-dopa is often used for the treatment of amblyopia and achieved some success. However, the L-dopa has some disadvantages such as side effects, more poor tolerance, and effects of instability. We obtained L-dopa methyl ester (LDME) through the structural transformation of L-dopa. The main purpose of this study was to observe the effects of LDME on the treatment of strabismic amblyopic cats. Effects of the LDME were evaluated and the possible mechanisms were discussed.
     Methods: 30 normal kittens were randomly divided into 6 groups: low dose of L-dopa methyl ester (20mg/kg), medium dose of L-dopa methyl ester (40mg/kg), and high dose of L-dopa methyl ester (80mg/kg,), positive control (L-dopa 40mg/kg), normal control, and model control groups. The surgery for producing iatrogenic convergent strabismus was performed on 4 week old kittens (normal control group excluded). After the confirmation of the development of amblyopia by pattern visual evoked potential, L-dopa methyl ester, L-dopa and normal saline were given to the corresponding animals respectively, once daily continuously for 30 days.
     In order to study the impact of levodopa methyl ester on the of function of cat visual cortex, we observed the pattern visual evoked potential (PVEP) change with visual electrophysiology instrument. The morphological change of the visual cortex was investigated by the HE stain, nissl stain and transmission electron microscope. The c-fos mRNA expression of visual cortex area 17 was detected with the technology of in situ hybridization. C-fos protein expression in the visual cortex area 17 was detected by immunohistochemistry. We had observed nerve growth factor (NGF) expression in the visual cortex area 17 by immunohistochemical technique. NOS immunocytochemstry staining method was applied accordingly to observe the changes of distribution and cells density across the visual cortex under the light microscope.
     Results:
     (1) The visual electrophysiology of strabismic amblyopia cats.
     The change in model control group (MC) was characterized by P100 amplitude reduction and P100 latency extension. P100 latency delayed in MC, latency was more longer than the contralateral eyes and the eyes in NC, the difference was significant (P<0.05). Compared with the same self normal eyes and the ipsilateral eye in NC, P100 amplitude in MC decreased significantly (P<0.01). After treatment, compared with the MC, P100 latency was reduced to varying degrees, and P100 latency of high-dose group was the most significant, which was statistically significant (p<0.01). After treatment with LDME, the amplitude increased, and there was no significant difference (p>0.05) when LDMEH was compared with the normal control group, suggesting that L-dopa methyl ester can significantly improve conduction and sensory function in model of strabismic amblyopia cats.
     (2) The morphological findings of strabismic amblyopia cats.
     In the MC, the neurons in the visual cortex area 17 were showed dysfunctionly, but the neurons of LDMEH, LDMEM, LDMEL and PC showed recovering signs, the restoration of LDMEH was more well than PC, LDMEM, and LDMEL. The inner particles and particle outer were recovered.
     (3) The influence of LDME on c-fos mRNA expression in the visual cortex area 17 of strabismic amblyopia cats.
     In the 17 area of the visual cortex of NC, the c-fos mRNA positive cells were widely distributed, and expressed actively. the distribution of hybrid cells: the densities ofⅡ/ⅢandⅤ/Ⅵlayer were higher, the density ofⅣlayer lowest. Compared with the normal control group, in the 17 area of the visual cortex of MC, the c-fos mRNA positive neurons were decreased in all layers, and the difference was significant (P<0.01). Compared with the model group, in the treatment group (including the PC, LDMEL, LDMEM, LDMEH) c-fosmRNA positive cells in the visual cortexⅡ/Ⅲ,Ⅳ, andⅤ/Ⅵlayers were increased. Except inⅣ, there was a significant (P<0.05 or P<0.01) in the other differences between the groups.
     (4) The influence of LDME on Fos expression in the visual cortex area 17 of strabismic amblyopia cats.
     The Fos positive cells, which nucleus showed dark brown, were seen in the whole floor of visual cortex area 17 of the NC cat. The density of the positive cells in layerⅡ,ⅢandⅥwas higher than that in layerⅣandⅤ. The distribution patterns of Fos positive cells between layers were similar to the NC, but the density of positive cell in each layer was significantly lower than that in NC, and the difference was statistically significant (P<0.01). In the treatment group (including the positive control group, L-dopa methyl ester of high, medium and low-dose group) the distribution of positive cells was basically in layer II, III, V and VI, but the density in each layer of the treatment group was more higher than that in model control group, and the difference was significant (P<0.05). Compared with PC, the density of Fos positive cells in each layers of LDME treatment group was more hiher than that in PC respectively, and some layers had statistical significance.
     (5) The influence of LDME on NGF expression in he visual cortex area 17 of strabismic amblyopia cats.
     Compared with the NC, the number density of NGF-immunoreactive cells in MC was reduced, and there was a significant difference between the two groups (p<0.01). Compared with MC, the number density of NGF-immunoreactive cells in each layers of the treatment group (including the PC, L-dopa methyl ester of high, medium and low-dose groups) was increased correspondingly, and the differences were statistically significant (p<0.01 or p<0.05) in addition to LDMEL inⅢ,ⅤandⅥ. Compared with the positive control group, the number density of NGF-immunoreactive cells in each layer of L-dopa methyl ester group was in the upward trend, and the differences in layerⅢandⅥof the LDMEH were statistically significant (p<0.01 or p< 0.05). Compared with NC, the number density of NGF-immunoreactive cells in LDMEH was less than that in the normal group, but there was no statistical difference between the two groups (p>0.05).
     (6) The influence of LDME on NOS expression in the visual cortex area 17 of strabismic amblyopia cats.
     The NOS positive cells in the NC were mainly distributed in the gray matter of theⅡ,Ⅲ,Ⅳ,ⅤandⅥlayers and white matter, the number of the NOS positive cells inⅡ/Ⅲwas highest,Ⅴ/Ⅵnext, andⅣat least. The distribution pattern of NOS-positive cells in visual cortex area 17 of MC cats was similar to that of the normal control group, however, within each layer and interlayer the NOS-positive fibers were significantly reduced, and the NOS-positive cell density was also significantly decreased (P<0.05). In the treatment group (including the positive control group, high low-dose L-dopa methyl ester groups) the NOS-positive cell density in each layers was increased, and the LDMEH was most obvious.
     Conclusions:
     (1) LDME can shorten the peak latency of P100 and increase P100 amplitude in strabismic amblyopia cats, and make them to recover to normal level, which can improve the function of conduction and perception in strabismic amblyopia cats eyes.
     (2) LDME has good therapeutic effect on the injured neuron in strabismic amblyopic cats, and can restore the neuron morphology. It also can promote the replication, transcription process, protein synthesis, protuberance of the neurons, and the synaptic transmission.
     (3). LDME can promote c-fos mRNA expression in area 17 of visual cortex of strabismic amblyopia cat.
     (4) LDME can promote Fos protein expression in area 17 of visual cortex in strabismic amblyopia cat.
     (5) LDME ester can increase NGF synthesis and release in area 17 of visual cortex in strabismic amblyopia cat. NGP expression coincides with of the change the PVEP. It is proved that LDME can improve the visual function of strabismic amblyopia cats eyes in certain degree. As a regulatory factor in cell function NGP may be play an important role on developmental plasticity in the visual system.
     (6) LDME can increase the nitric oxide levels in area 17 of visual cortex of strabismic amblyopia cats to some extent.
     (7) LDME has therapeutic effects on the strabismic amblyopic cats, and its mechanism may be related to the increases in NGF synthesis and release and the nitric oxide level in visual cortex area 17 of strabismic amblyopic cats.
引文
[1] Whittle EJ, bryans c, timeny b. visual acuity in esotropic cats folloeing occlusion of the non-deviating eye[J]. Behav Brain Res, 1987, 24(2): 101-9.
    [2] Jones KR, Kalil RE, Spear PD. effects of strabismus on responsivity spatial resolution and contrast sensitivity of cat lateral geniculate neurons[J]. J Neurophysiol, 1984, 52(3): 538-52.
    [3] Lynne Kior, Pesand Suzanne, P Mekee. Neural mechanisms underlying ambl-yopia.Current Opinion in Neurobiology, 1999, 9: 480-486.
    [4] LeviDM, Manny RE. The pathophysiology of amblyopia: electrophysio logical studies[J]. Ann NYA cad Sci 1983, 388: 243-263.
    [5] Deng DM, Long SX, Mai GH, et al. Effect of levodopa on visual evoked potential in amblyomia[J]. Eye Science, 1997, 13: 182-185.
    [6] Mohan K, DhankarV, Sharma A. Visual acuities after levodopa administration in amblyopia[J]. J Pediatr Ophthalmol Strabismus. 2001, 38: 62-67.
    [7] Wu LZ, Wu DZ. Clinical visual electrophysiology[M]. BeiJing: Science Publing House. 1999:362.
    [8] Ma KM, Xu BL, Liu LL, et al. The evalution on the picture visual evoked potentials in dialgnosis of children with amblyopia[J]. China Modern Doctor, 2007, 45(13): 4-5.
    [9] Cleland GB, Crew ther DP. Normality of spatial resolution of retinal ganglion cells in cats with strabismic amblyopia[J]. J Physiol 1982, 326: 235-249.
    [10]杨崇清,马丽卿.视觉诱发电位在弱视发病机制研究中的应用[J].浙江医学,1999,21(10):636-637.
    [11] Snyder A and Shapley R. Deficits in the visual evoked potentials of cats as a result of visual deprivation[J]. Exp Brain Res, 1979, 37: 73-86.
    [12] Vernon Odom, Miehael Baeh, Colin Barber, etal. Visual Evoked Potentials Standard. 2004.
    [13]严宏.弱视学,第1版[M].科学出版社,2007.
    [14] Sehmidt KE, Singer W, Galuske RA. Proeessing deficits in Primary visual cortex of amblyopia cats.J Neurophysiol, 2004, 91(4): 1661-71.
    [15] Chung W, Hong S, Lee JB, Han SH. Pattern visual evoked potential as a predictor of occlusion therapy for amblyopia[J]. Korean J Ophthalm, 2008, 22(4): 251-4.
    [16] Stankovic B, Milenkovic S. Continuous full-time occlusion of the sound eye vs full-time occlusion of the sound eye periodically alternating with occlusion of the amblyopic eye in treatment of amblyopia: a prospective randomized study[J]. Eur J Ophthalmol, 2007, 17(1): 11-9.
    [17] Ridder WH 3rd, Rouse MW.Predicting potential acuities in amblyopes predicting post-therapy acuity in amblyopes[J]. Doc Ophthalmol, 2007, 114(3): 134-45.
    [18]许娜,李平华.斜视性弱视发病机制的研究进展[J].国际眼科杂志,2006,6(5):11 39-1142.
    [19]华山,肖满意,李荡萍,唐罗生.儿童图形翻转视觉诱发电位对远视性弱视视功能研究[J].国际眼科杂志,2006,6(3):647-648.
    [20] Srebro, R. Visually evoked potentials in eccentrically and centrally fixing amblyopes[J]. Br J Ophthalmol, 1984. 68(7): 468-471.
    [21] Goodyear BG. BOLD fMRI response of early visual areas to perceived contrast in human amblyopia[J]. J Neurophysiol, 2000, 84(4): 1907-1913.
    [22] Weiss A, K.J. VEP correlations with anisometropic and strabismic amblyopia in children before and after patching[J]. Invest Ophthalmol Vis Sci, 2002, 43: 2940.
    [23] Payne BR, Cornwell P. System-wide repercussions of damage to the immature visual cortex[J]. Trends Neurosci, 1994, 17: 126-130.
    [24]张作明,郭守一,骆阁大,等.临床视觉电生理学检查37210例分析[J].眼视光学杂志[J],2002,4(2):75-77.
    [25]盛迅伦,庄文娟,都淑红.儿童单眼视力缺陷的图形视觉诱发电位分析[J].临床眼科杂志,2002,10(3):217-220.
    [26] Das T, Kundus S, Mazumdar AK, etal. Studies on central nervous system function in diabetes mellitus[J]. J Indian Med Assoe, 2001, 99(2): 84-89.
    [27]黄仲委,余杨,王燕糖,等.糖尿病性视网膜病变的图形[J].眼科视光学杂志,2001,3(3):169-171.
    [28]李惠玲,金婉容,崔惠贤,等.儿童弱视PVEP和VEOG的检测[J].中国斜视与小儿眼科杂志,1999,7(3):115-118.
    [29] Akabane A, Saito, Suzuke Y, etal. Monitoring visual evoked Potentials during retraction of the canine optic nerve :protective effect of unroofing the optic canal.J Neurosing, 1995, 82(2): 284-287.
    [1] Lowel S. Ocular dominance colum development: strabismus thespacing of adjacent columns in cat visual cortex[J]. J Neurosci, 1994, 14 (12): 7451-7468.
    [2] Tychsen L, Burkhalter A. Functional and structural abnormalitiesin visual cortex in early childhood strabismus[J] . Klin Monatsbl Augenheilkd, 1996, 208(1): 18-22.
    [3] Fenstemaker SB, Kiorpes L, Movshon JA. Effects of experimental strabismus on the architecture of macaque monkey striate cortex[J]. J Comp Neurol. 2001, 438(3): 300-317.
    [4] Wong AM, Burkhalter A, Tychsen L. Suppression ofmetabolic activity caused byinfantile strabismus and strabismic amblyopia in striate visual cortex of macaquemonkeys[J]. JAAPOS, 2005, 9(1): 37- 47.
    [5] Crawford ML, von Noordn GK. The effects of short-term experimental strabismus on the visual system in Macaca mulatta[J]. Invest Ophthalmol Vis Sci, 1979, 18: 496-498.
    [6] Crewther SG. Neural site of strabismic arnblyopia in cats: X-cell acuities in the LGN[J]. Exp Brain Res, 1988, 72: 503-509.
    [7]郑汉,阴正勤.斜视性弱视猫视中枢神经元细胞色素氧化酶活性变化[J].第三军医大学学报,2000,22(6):561-564.
    [8]坤英赵堪兴林锦镛.左旋多巴对弱视猫视皮质区神经细胞的影响[J].中国斜视与小儿眼科杂志,2004,12(4):150-155.
    [9] Jiang ML, Han TZ, Yang DW, etal. Morphological alteration of the hippocampal synapses in rats prenatally exposed to magnetic resonance imaging magnetic fields[J]. Acta Physiologica Sinica,2003,55(6):705-710.
    [10]徐晓虹,章子贵.葛根素对D-半乳糖致衰老小鼠记忆行为和海马突触结构的影响[J].药学学报,2002,37(1):1-4.
    [11] Briones TL, Suh E, Jozsa L, etal. Behaviorally induced synaptogenesis and dendritic growth in the hippocampal region following transient global cerebral ischemia are accompanied by improvement in spatial learning[J]. Experimental Neurology, 2006,19(2):530-538.
    [12]张紫福,杨正伟,李坤,等.海马CA1区穿孔突触数与联合学习成绩优良相关性[J].解剖学杂志,2004,27(4):398-400.
    [13]徐晓虹.葛根素注射液对慢性乙醇中毒小鼠记忆障碍的改善作用[J].中国药学杂志,2003,38(1):31-34.
    [14] Nakanishi N, Axel R, Shneicber NA. Alternative splicing generatesfunctionally distinct N-methyl-D-aspartate receptors[J]. ro Natl Sci USA. 1992, 89: 8522-8556.
    [15] Quinlan EM, et al. Rapid experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo[J]. Nat Neurosci 1992, 2(4): 352-357.
    [16] Pesavento E, Margotti E, et al. Blocking the NGF-trkA InteractionRescues the developmental Loss of LTP in the rat visual cortex:role of the cholinergic system[J]. Neuron, 2000, 25: 165-175.
    [17]阴正勤,邓泽明,陈莉,等. N-甲基-D-天门冬氨酸-R1不同mRNA构型在斜视性弱视猫视皮层的表达[J].中华眼底病杂志,2000,16(2):34 -38.
    [18] CaricD, PriceDJ. Evidence that the lateral geniculate nucleus regulates thenormal development of visual corticocortial projections in the cat[J]. Exp Neurol, 1999, 156(2): 353-362.
    [19] Fox KA. Critical period for experience-dependent synaptic plasticity in rat barrel cortex[J]. J Neurosci, 1992, 12: 1826-1838.
    [20]Cao Z. Postnatal development of NR1, NR2A, and NR2B immunoreactivity in the visual cortex of the rat[J]. Brain Res. 2000, 859(1): 26-37.
    [21] Fresina M, Dickmann A, Salerni A, De Gregorio F, Campos EC. Effect of oral CDP-choline on visual function in young amblyopic patients[J].Graefes Arch Clin Exp Ophthalmol. 2008, 246(1): 143-150.
    [22] Mitchell DE. A special role for binocular visual input during development and as a component of occlusion therapy for treatment of amblyopia[J]. Restor Neurol Neurosci.2008, 26(4-5): 425-434.
    [23] Gianfranceschi L, Siciliano R, Walls J. Visual cortex is rescued from the effects of dark rearing by overexpression of BDNF. Proc Natl Acad Sci USA, 2003, 100(21): 12486-12491.
    [24]邵立功,章应华,张东杲,等.弱视猫视皮质17区神经元c-fos基因表达特性的研究[J].中华眼科杂志,1993,29(6):366-370.
    [25] Bredt DS, Snyder SF. Nitric oxide a physiological messenger Molecule[J]. Annu Rev Biochem, 1994, 63: 175-178.
    [26] J.Garthwaite, C.L.Boulton. Nitric oxide signaling in the cental nervous system[J]. Annu.Rev.Physiol. 1995, 57: 683-706.
    [27] J.Cudeiro, C.Rivadulla. Sight and insight-on the physiological role of nitric oxide in the visual system[J]. Trends Neurosci, 1999, 22: 109-116.
    [28] Joshua T. Rapid Anatomical Plasticity the developing Visual Cortex[J]. Horizontal Connections in Neurosci, 2001, 21(10): 3476-3482.
    [1] Keyser SM. The induction of gene expression in manmalian cell by Radiation[J]. Semin Cancer Biol, 1993, 4: 119-128.
    [2] Sagar SM, Sharp FR, Curran T. Expression of c-fos protein in brain: metabolic mapping at the cellular level[J]. Science, 1988, 493: 391.
    [3] Kaczmarek L, Chaudhuri A. Sensory regulation of immediate-early gene expression in mammalian visual cortex: implications for functional mapping and neuralp lasticity[J]. Brain Res Bev, 1997, 23(3): 237-256
    [4] Titze-de-Almeida R, Lino-de-Oliveira C, Shida HW, Guimar?aes FS, Del Bel EA. Midazolam and NMDA receptor antagonist 2-amino-7- phosphoheptanoic acid (AP7) attenuate stress-induced expression of c-fos mRNA in the dentate gyrus. Cell Mol Neurobiol 1994, 14: 373-80.
    [5] Wan W, Wetmore L, Sorensen CM, Greenberg AH, Nance DM. Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain. Brain Res Bull 1994, 34: 7-14.
    [6] Estel Van der Gucht, Ann Massie, Bert De Klerck. M olecular cloning and differential expression of the cat immediate early gene c-fos[J]. Molecular Brain Research, 2003, 111: 198-210.
    [7] Cleland GB, Crew ther DP. Normality of spatial resolution of retinal ganglion cells in cats with strabismic amblyopia [J]. J Physiol 1982, 326: 235-249.
    [8] Wan X Y, Luo M, He P, et al, Effect of matrine and oxymatrine on induction of differentiation of human hepatoma carcinoma cell line in vitro[J]. Chinese Pharmacological Bulletin, 2009, 25(7): 977-979.
    [9] Zhang F, Halleux P, A rckens L, Van DuffelW, Van BreeL, M ailleux P, et al. Distribution of immediate early gene zif-268, c-fos, c-jun and jun-D mRNA in the adult cat w ith special references to brain region related to vision[J]. Neurosci Lett 1994, 176(2): 137-141.
    [10] Rosen KM, Mcormack MA, Villa-Komaroff L, Mower GD. Brief visual experience induces immediately early gene expression in the cat visual cortex[J]. Proc Natal A cad Sci USA. 1992, 89(12): 5437-5441.
    [11] Nakanishi N, Axel R,Shneicber NA. Alternative splicing generates functionally distinct N-methyl-D-aspartate receptors[J]. Pro Natl Sci USA. 1992, 89: 8522-8556.
    [12] Quinlan EM, etal. Rapid experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo[J]. Nat Neuroscil, 1992, 2(4): 352-357.
    [13]严宏.弱视学,第1版.科学出版社,2007.
    [14]阴正勤,余涛,陈莉.斜视性弱视猫发育过程中视皮质NMDA-R1表达的免疫组织化学电镜观察[J].中华眼科杂志,38(8):472-475.
    [15] Mower GD. Differences in the induction of Fos protein in cat visual cortex during and after the critical period[J]. Brain Res MolBrain Res, 1994, 21(12): 47-54.
    [16] Mower GD, Kaplan IV. Fos expression during the critical period in visual cortex:differences between normal and dark reared cats[J]. Brain Res Mol Brain Res 1999, 64(2): 264-269.
    [17] Blanchard DC, Canteras NS, Markham CM, Pentkowski NS, Blanchard RJ.Lesions of structures showing FOS expression to cat presentation: effects on responsivity to a cat, cat odor,and nonpredator threat[J]. Neurosci Biobehav Rev 2005, 29(8): 1243-53.
    [1]卢静,戴体俊,曾因明. c-fos基因表达的相关机制及和意义[J].国外医学麻醉学与复苏分册,2004,25(5):273-275.
    [2] Leszek k. Sensory regulation of immediate-early gene expression in mammalian visual cortex: implications for functional mapping and neural plasticity[J]. BrainRes Brain Res Rev, 1997, 23(3): 237-56.
    [3] Hughes P. Induction of immediate-early genes and the control of neurotransmitter-regulated gene expression within the nervous system[J]. Pharmacol Rev, 1995, 47(1): 133-78.
    [4] Dragunow M. The use of c-fos as a metabolic marker inneuronal pathway tracing[J]. Neurosci. Methods, 1989, 29: 261-265.
    [5] Hunt SP, Pini A, Evan G. Induction of c-Fos-like protein in spinal cord neurons following sensory stimulation[J]. Nature, 1987, 328: 632-634.
    [6] Sagar SM. Expression of c-fos protein in brain:metabolic mapping at the cellular level[J]. Science, 1988, 240: 1328-1331.
    [7] Mower GD. Differences in the induction of Fos protein in cat visual cortex during and after the critical period[J]. Brain Res Mol Brain Res, 1994, 21(1-2): 47-54.
    [8] Rosen KM. Brief visual experience induces immediate early gene expression in the cat visual cortex[J]. Proc Natl Acad Sci USA, 1992, 89(12): 5437-5441.
    [9] Chapman B. Ocular dominance shift in kitten visual cortex caused by imbalance in retinal electrical activity[J]. Nature, 1986, 324(6093): 154-156.
    [10] Sagar SM, Sharp FR, Curran T. Expression of c-fos protein in brain: metabolic mapping at the cellular level[J]. Science, 1988, 493: 391.
    [11] Hughes P. Induction of immediate-early genes and the control of neurotransmitter-regulated gene expression within the nervous system[J]. Pharmacol Rev, 1995, 47(1): 133-178.
    [12] Kaplan IV. Immediate early gene expression in cat visual cortex during and after the critical period: differences between EGR-1 and Fos proteins[J]. Brain Res Mol Brain Res, 1996, 36(1): 12-22.
    [13] Vanessa Beijamini, Francisco Silveira Guimaraes.c-Fos expression increase in NADPH-diaphorase positive neurons after exposure to a live cat[J]. Behavioural Brain Research, 2006, 170: 52-61.
    [14] Jensen FE, Differences in c-fos immunoreactivity due to age and mode of seizure induction[J]. Brain Res Mol Brain Res, 1993, 17(3-4): 185-93.
    [15] Hubel DH.Binocular interaction in striate cortex of kittens reared with artificial squint[J]. Neurophysiol, 1965, 28 (6): 1041-1 059.
    [16] Daw NW. Critical period for monocular deprivation in dark reared cats[J]. Neurophysiol, 1992, 67: 197-203.
    [17] Estel Van der Gucht, Ann Massie, Bert De Klerck. Molecular cloning anddifferential expression of the cat immediate early gene c-fos[J]. Molecular Brain Research 2003, 111: 198-210.
    [18] LeVay. The development of ocular dominance columns in normal and visually deprived monkeys[J]. CompNeurol, 1980, 191: 1-51.
    [19] Mower G.D. Dark rearing prolongs physiological but not anatomical plasticity of the cat visual cortex[J]. Comp. Neurol, 1985, 235: 448-466.
    [20] Singer W. Evidence for long term functional plasticity in the visual cortex of adult cats[J]. Physiol, 1982, 324: 239-248.
    [21] Beaver CJ, Mitchell DE, Robertson HA etal. Immunohistochemical study of the pattern of rapid expression of c-fos protein in the visual cortex of dark-reared kittens following initial exposure to light[J].Comp Neurology, 1993, 333: 469-484.
    [22] Estel Van der Gucht, Stefan Clerens, Sandy Jacobs, etal. Light-induced Fos expression in phosphate-activated glutaminase and neurofilament protein- immunoreactive neurons in cat primary visual cortex[J]. Brain Research, 2005, 1035: 60-66.
    [23]阴正勤.单眼内斜幼猫空间分辨力发育的P-ERG和P-VEP分析[J].眼底病,1992,(2):65-71.
    [24]邵立功.弱视猫视系三级神及突触的超微结构研究[J].中华眼科杂志,1994,(1):53-56.
    [25] Ronald E. Response properies of striate cortex neurons in cats raised with divergent or convergent strabismus[J]. Neurophysiol, 1984, 52(3): 514-537.
    [26] Sunghee Cho, Eun-Mi Park, Yoonseong Kim. Early c-Fos Induction After Cerebral Ischemia: A Possible Neuroprotective Role[J]. Journal of Cerebral Blood Flow and Metabolism, 2001, 21: 550-556.
    [27] Chino YM. Effects of rearing kittens with convergent strabismus ondevelopment of receptive-field properties in striate cortex neurons[J]. Neurophysiol, 1983, 50(1): 265-286.
    [28] Eggers HM. Spatial frequency selectivity of cells in macaque visual cortex[J]. Invest Ophthalmol Vis Sci, 1984, 25: 278-286.
    [29] Gabriella Sekerkova, Ema Ilijic, Enrico Mugnaini, etal. Otolith organ or semicircular canal stimulation induces c-fos expression in unipolar brush cells and granule cells of cat and squirrel monkey[J]. Exp Brain Res 2005, 164: 286-300.
    [30]李凡,舒斯云,包新民.多巴胺受体的结构和功能[J].中国神经科学杂志,2003,19:405-410.
    [31]张厚亮,任惠民,王坚等.光照对视网膜色素上皮细胞分泌多巴胺功能的影响[J].中国临床神经科学,2007,15:123-128.
    [32] Fosse VM, etal. Postnatal development of glutamatergic, GABAergic, and cholinergic neurotransmitter phenotypes in the visual cortex, lateral geniculate nucleus, pulvinar, and superior colliculus in cats[J]. Neurosci, 1989, 9(2): 426-35.
    [33] Chen L, Developmental changes in the expression of GABA(A) receptor subunits (alpha(1), alpha(2), alpha(3)) in the cat visual cortex[J]. Brain Res Mol Brain Res, 1988, 56(1-2): 135-43.
    [34] BryansC. The role of binocular competition in strabismic amblyopia in cats, J. Physiol, 1985, 367, 25-31.
    [35] Crewther SG. Amblyopia and suppression in binocular cortical neurones of strabismic cat[J]. Neuroreport, 1993, 4(9): 1083-1086.
    [36] Wiesel TN, Hubel DH. Receptive fields of cells in striate cortex of very young visuallly in experienced kittens[J]. Neurophysiol, 1963, 26: 994-1002.
    [37] Crawford ML, von Noordn GK. The effects of short-term experimental strabismus on the visual system in Macaca mulatta. Invest Ophthalmol Vis Sci, 1979, 18: 496
    [38] Reis RAM, Ventura ALM, Kubrusly RCC, etal. Dopaminergic signaling in the developing retina[J]. BrainResearch Reviews, 2007, 54: 181-188.
    [39]杨丽萍,艾育德,王秀英.多巴胺治疗弱视的神经生理机制[J].内蒙古医学院学报,1999,21(4):283-285.
    [40]蔡浩然.视觉发育敏感期机理研究的新进展[J].中国斜视与小儿眼科杂志,1994,2:178-182.
    [41]张方华.我国弱视与斜视防10年进展[J].中华眼科杂志,2000,36:208-211.
    [1]彭形.神经生长因子生物学效应的研究进展[J].检验医学与临床,2009,6(3):203-205.
    [2]邵立功.弱视模型视觉神经系统的神经生长因子表达特征研究[J].海军总医院学报,200,19(4):212-217.
    [3]毛俊峰,刘双珍,秦文娟.左旋多巴对豚鼠形觉剥夺性近视形成的影响[J].眼科研究,2009,27(4):257-261.
    [4] Hannila SS, Kawaja MD. Nerve growth factor mediated collateral sp routing of central sensory axons into deafferentated of the dorsal hom is enhanced in the absence of the p75 neurotrophin in receptor[J]. Comp Neurol, 2005, 486(4): 331-343.
    [5] Ernfors P, Tbanez C, Ebendal T, etal. Molecular cloning and neurotrophic activities of a protein with structural similarities tonerve growth factor:developmental and topographical expression in the brain[J]. Proc Natl Acad Sci USA, 1999, 87: 545-548.
    [6] Levi MR.The nerver growth factor 35 years later[J]. Science, 1987: 1154 -1162.
    [7]邵立功,郭静秋.不同时限单眼斜视和剥夺猫视觉系统的神经生长因子表达研究[J].眼科,2000,9(3):181-190.
    [8]邵立功,郭静秋.不同时限单眼斜视和剥夺模型猫视觉系统神经元的神经营养因子-3表达机理研究[J].中国斜视与小儿眼科杂志,1999,7 (4):175-183.
    [9] Domnenici L, Fontanesi G, Cattanco A, et al. Nerve growth factor (NGF) up take and transport following injection in the develop ing rat visual cortex[J]. Vision Neurosci, 1994, 11: 1093.
    [10] Berandi N. ProR Soc Sci, 1993, 251: (17): 1330.
    [11] Li Y, Holtzman DM, Kromer LF, etal. Regulation of trkA and ChAT expression in developing rat basal forebrain: evidence that both exogenousand endogenous NGF regulate differentiation of cholinergic neurons[J]. Neurosci, 1995, 15: 2888-2905.
    [12] Knipper M, Leung LS, Zhao D, etal. Short term modulation of glutamatergic synapses in adult rat hippocampus[J]. Neuroreport, 1994, 5: 2433-2436.
    [13] Shatz CJ. Impulse activity and the patterning of connections during CNS development[J]. Neuron, 1990, 5: 745-756.
    [14] Galli L, Maffei L. Spontaneous impulse activity of rat retinal ganglion cells in prenatal life[J]. Science, 1988, 242: 90-91.
    [15] Starkey GD, Petratos S, Shipham KA, etal. Neurotrophin receptor expression and responsiveness by postnatal cerebral oligodendroglia[J]. Neuroreport, 2001, 12(18): 4081-4086.
    [16] Shatz CJ, StrykerMP. Ocular dominance in layer IV of the cats visual cortex and the effects of visual deprivation[J]. Physiol, l978, 281: 267-283.
    [17] Levay S, Ferster D. Proportion of interneurons in the cat's lateral geniculate nucleus[J]. Brain Res, 1979, 23(164): 304-308.
    [18] Ferster D, Levay S. The axonal arborizations of lateral geniculate neurons in the striate cortex of the cat[J]. Comp Neurol, 1978, 182: 120.
    [19] Domnenici L, Fontanesi G, Cattanco A, etal. Nerve growth factor (NGF) up take and transport following injection in the develop ing rat visual cortex[J]. Vision Neurosci, 1994, 11: 1093-1095.
    [20] Carmignoto G, CaneHa R, Candeo P, et al. Effect of nerve growth factoron neuronal p lasticity of the kitten visual cortex[J]. Physiol, 1993, 464: 343-360.
    [21] Cattaneo A, Rapposelli B, Calissano P. Production of monoclonal antibodied against nerve growth factor[J]. Neurochem, 1988, 50:1003-1010.
    [22] Mohan K, Dhankar V, Sharnma A. Visual acuities after levodopa administration in amblyopia[J]. Pediatr Ophthalmol Strabismus, 2001, 38(2): 62-67.
    [23] ReisRAM,Ventura AM, Kubrusly RC, etal. Dopaminergic signaling in the developing retina[J]. Brain Research Reviews, 2007, 54: 181-188.
    [24] Dorenbos R, Contini M, Hirasawa H, etal. Expression of circadian clock genes in retinal dopaminergic cells[J]. Vis Neurosci, 2007, 24: 573- 580.
    [25]郑煜,黎晓新,牛兰俊.左旋多巴对形觉剥夺性弱视猫视皮层17区神经生长因子的影响[J].眼科研究,2009,27(11):989-993.
    [26]于湛,胡聪,梁敏.猫斜视性弱视治疗前后视皮质17区神经生长因子的表达[J].中国实用眼科杂志,2004,22(3):229-223.
    [1] Bredt DS, Snyder SH. Nitric oxide, a novel neuronalmessenger[J]. Neuron, 1992, 8: 3-11.
    [2]高建华,张东杲.一氧化氮与视觉[J].中国实用眼科杂志, 2001, 19(5): 32 3-325.
    [3] Garth waite J, Charles SL, Chess Williams R. Endo thelium-derived relaxing factor release on activation of NMDA receptors suggests role as intracellular messenger in the brain[J]. Nature, 1998, 336: 385-388.
    [4] Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. TNS, 1991, 14: 60-67.
    [5]刘燕,张东杲.剥脱性弱视大鼠中枢一氧化氮合酶阳性神经分布与数量的变化[J].第四军医大学学报,1997,18(4):357-360.
    [6]高建华,张东杲.宫枢政一氧化氮合成酶在正常幼猫视觉系统的分布[J].眼科研究,2000,18(1):22-24.
    [7]蒋斌,丁锦东,周逸峰.猫视皮层17区一氧化氮合酶阳性神经元的生后发育[J].神经解剖学杂志,1999,15(3:222-226.
    [8] Valtschanoff JG. Neurons in rat cerebral cortex that synthesize nitric oxide and NADPH-diaphorase histochemistry NOS immuno-cytochemistry and colocalitation with GABA[J]. Neurosci Lett, 1993, 157(2): 157-159.
    [9] Cudeiro J, Rivadulla C, Rodriguez R, et al. Modulatory influence of putative inhibitors of nitric oxide synthesis on visual processing in the cat lateral geniculate nucleus[J]. Neurophysiology, 1994, 71(1): 146-150.
    [10] Cramer KS, Sur M. Inhibition of nitric oxide synthase disrupts on/off sublamination in the ferrect lateral geniculate nucleus[J]. Soc Neurosci Abst, 1994, 20: 1470-1472.
    [11] Galuske RA, Kim DS,Castren E, et al. Brain-derived neurotrophic factorreversed experience-dependent synaptic modifications in kitten visual cortex[J]. Eur J Neurosci, 1996, 8: 1554-1559.
    [12] BartschAP, Van Hemmen JL. Combined Hebbian development of geniculocortical and lateral connectivity in a model of primary visual cortex[J]. Biol Cybern, 2001, 84: 41-55.
    [13]高朋芬,阴正勤,刘应兵,等.大鼠视觉发育可塑性关键期视皮层LTP的研究[J].中国神经科学杂志,2002,18:699-703.
    [14]王仁刚,朱兴族.一氧化氮在神经系统中的作用[J].生理科学进展,1994,25:73-75.
    [15] Gonzalez-Forero D, Portillo F, Gomez L, et al. Inhibition of resting potassium conductances by long2term activation of the NO/cGMP/protein kinase G pathway: a new mechanism regulating neuronal excitability[J]. J Neurosci, 2007, 27(23): 6302-6312.
    [16] Shih CD, Chuang YC. Nitric oxide and GABA mediate bi-directional cardiovascular effects of orexin in the nucleus tractus solitarii of rats[J]. Neuroscience, 2007, 149(3): 625-635.
    [17] Finney EM, Stone JR, Shatz CJ. Major glutamatergic projection from subplate into visual cortex during development[J]. J Comp Neurol, 1998, 398: 105-118.
    [18]邵立功,章应华,张东杲,等.弱视猫视皮质17区神经元c-fos基因表达特性的研究[J].中华眼科杂志,1993,29(6):366-370.
    [19] Bredt DS, Snyder SF. Nitric oxide a physiological messenger Molecule [J]. Annu Rev Biochem, 1994, 63: 175-178.
    [20] J.Garthwaite, C.L.Boulton. Nitric oxide signaling in the cental nervous system[J]. Annu Rev. Physiol. 1995, 57: 683-706.
    [21] J.Cudeiro, C. Rivadulla. Sight and insight-on the physiological role ofnitric oxide in the visual system[J]. Trends Neurosci, 1999, 22: 109-116.
    [22] Reiter HO, Waitzman DM, Stryker MP. Cortical activity blockade prevent ocular dominance plasticity in the kitten[J]. Exp Brain Res, 1986, 65: 182-188.
    [23] HataY, StrykerMP. Control of thalamo cortical afferent rearrangment by postsynaptic activity in developing visual cortex. Science, 1994, 265: 1732-1735.
    [24] BearMF, Kleinschmidt A, GuQ, etal. Distribution of experience dependent synaptic modification in striate cortex by infusion of an NMDA receptor antagonist. J Neuro sci, 1990, 10: 909-925.
    [25] Kandel ER, ODell TJ. A readult learning mechanism s also used for development [J]. Science, 1992, 258: 243-245.
    [26] Izumi Y, Clifford DB, Zorum ski CF. Inhibition of longterm potentiation by NMDA-mediated nitric oxide release[J]. Science, 1992, 257: 1273-1276.
    [27] Shibuki K, Okada D. Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum[J]. Nature, 1991, 394: 326-328.
    [28] HaleyJE, Wilcox GL, Chapman PF. The role of nitric oxide in hippocampal long-term potentiation. Neuron, 1992, 8: 211-216
    [29] Hope BT, Michael GJ, Knigge KM, etal. Neuronal NADPH-diaphorase is a nitric oxide synthase[J]. Proc Natl Acad Sci USA, 1991, 88: 2811-2814.
    [30]张亚娟,苏鸣,刘丽,等.单眼剥夺大鼠反缝治疗前后背外侧膝状体nNOS的免疫组织化学研究[J].中国斜视与小儿眼科杂志,2007,15(4):145-148.
    [31] Cudeiro J, Rivadulla C, Rodrignez R, etal. Application of l-Arg and L-NO-Arg modify cellular responses in the primary visual cortex of the cat[J]. Soc Neuro sciA bstr, 1995, 21: 1653-1656.
    [1] Ohlsson J, Villarreal G, Sjostrom A, etal. Visual acuity, residual amblyopiaand ocular pathology in a screened opulation of 12-13 year-old chidren in Sweden[J]. Acta Ophtelmol Scand, 2001, 79: 589-595.
    [2] Zaba JN, Johnson RA,Reynolds WT. Vision examinations for all children entering public school-the new Kentucky law[J]. Optometry, 2003, 74: 149-158.
    [3] Matsuo T, Matsuo C. The prevalence of strabismus and amblyopia in Japanese elementary school children[J]. Ophthalmic Epidemiol, 2005, 12: 31-36.
    [4]张庆慧.北京市大兴区学龄前儿童视力及弱视调查[J].国际眼科杂志, 2006, 6(6): 48.
    [5]江蕙芸,陈红慧,刘伟民.南宁市10784名幼儿园儿童视力状况调查[J].广西医科大学学报,2006,23(6):36-38.
    [6]卢秀珍,屈政朋,王桂敏,等.学龄前儿童弱视及斜视的调查[J].中国斜视与小儿眼科杂志,2006,(3):23-25.
    [7]美国眼科学会编.中华医学会眼科学分会编译.眼科临床指南.人民卫生出版社,2006年8月第1版,417-445.
    [8]赵堪兴,史学锋.新世纪我国斜视弱视研究进展[J].中华眼科杂志,2005,41(8):729-735.
    [9]孙久荣.脑科学导论[M].北京:北京大学出版社,2001:139-140.
    [10]王建军.神经科学探索脑[M].北京高等教育出版社,2004:303-319.
    [11]寿天德主编.神经生物学[M].北京:高等教育出版社,2001:59-186.
    [12] Xue JT, Ramoa AS, Carney T, Freeman RD. Binocular interaction in the dorsallateral geniculate nucleus of the cat. Exp Brain Res 1987, 68: 305-310.
    [13] Bassi CJ, Lehmkuhle S. Clinical implications of parallel visual pathways[J]. J Am Optom Assoc 1990, 61:98-110.
    [14] Bear MF, Connors BW, Paradiso MA. The central visual system. In: Satterfield TS, ed. Neuroscience: Exploring the Brain. altimore, Maryland: Williams& Wilkins, 1996: 240-270.
    [15] Rosenzweig MR, Leiman AL. Physiological Psychology. Lexington, Massachusetts: DC Heath and Company, 1982, 260.
    [16] Sherman SM, Koch C. The control of retinogeniculate transmission in the mammalian lateral geniculate nucleus[J]. Fxp Brain Res 1986, 63: 1-20
    [17] Sillito AM, Jones HE, Gerstein GL, West DC. Feature-linked synchronization of thalamic relay cell firing induced by feedback from the visual cortex[J]. Nature, 1994, 369: 479-482.
    [18] Daw NW. Visual Development. New York: Plenum Press, 1995: 17.
    [19]Bassi CJ, Lehmkuhle S. Clinical implications of parallel visual pathways[J]. J Am Optom Assoc 1990, 61: 98-110.
    [20]陈增爱. DTI和fMRI在正常成人视觉系统的联合应用研究[J].中国医学计算机成像杂志,2006,12(6):371-375.
    [21] Tong F.Primary visual cortex and visual awareness[J]. Nature Rev Neurosci, 2003, 4(3): 219-229.
    [22] Beck PD, Kaas JH. Thalamic connections of the dorsomedial visual area in primates[J]. J Comp Neurol 1998, 396: 381-398.
    [23] Wurtz RH, Goldberg ME. Activity of superior colliculus in behaving monkey. IV Effects of lesions on eye movements[J]. J Neurophysiol 1972; 35: 587-596.
    [24]王晶蕴,赵堪兴.视觉神经机制中同步振荡研究的新进展[J].眼科新进展,2002,22(2):139.
    [25]李速,齐翔林,胡宏,等.功能柱结构神经网络模型中的同步振荡现象[J].中国科学C辑生命科学,2004,34(4):385-394.
    [26] Felleman D, Van Essen D. Distributed hierarchical processing in the primate cerebral cortex. Cereb Cortex 1991, 1: 1-47.
    [27] Dreher B, Wang C, Turlejski KJ, Djavadian RL, Burke W. Area PMLS and 21a of cat visual cortex: two functional distinct areas. Cereb Cortex 1996, 6: 585-595.
    [28] Ungerleider LG, Courtney SM, Haxby JV. A neural system for human visual working memory[J]. Proc Natl Acad Sci USA, 1998, 95(3): 883-890.
    [29] Nicholls JG Martin AR, Wallace BG Fuchs PA. From Neuron to Brain, 4th edition. Sunderland, MA: Sinauer Associates, 2001.
    [30] Kastner S, Ungerleider LG. Mechanisms of visual attention in the human cortex[J]. Annu Rev Neurosci, 2000, 23: 315-341.
    [31] Sincich LC, Park KF, Wohlgemuth MJ, eta1. Bypassing V1: a direct geniculate inputto areaMT[J]. Nat Neurosci, 2004, 7(10): l123-1128.
    [32] Wang C, Dreher B. Binocular interactions and disparity coding in area 21a of cat extrastriate visual cortex[J]. Exp Brain Res 1996, 108: 257- 272.
    [33] Tootell RB, Nelissen K, Vanduffel W, et a1. Search for color’center(s)’in macaque visual cortex[J].Cereb Cortex,2004;14:353-363.
    [34] Tardif E, Bergeron A, Lepore F, Guillemot JP. Spatial and temporal frequency tuning and contrast sensitivity of single neurons in area 21a of the cat[J]. Brain Res 1996, 716: 219-223.
    [35] Dreher B, Michalski A, Ho RH, Lee CW, Burke W. Processing of form and motion in area 21a of cat visual cortex[J]. Vis Neurosci 1993, 10: 93-115.
    [36] Wang C, Waleszczyk WJ, Burke W and Dreher B. Modulatory influence of feedback projections from area 21a on neuronal activities in striate cortex of the cat[J]. Cereb Cortex, 2000; 10(12): 1217-1232.
    [37] Gril1, Spector K, Malach R. The human visual cortex[J]. Annu RevNeurosci, 2004, 27: 649-677.
    [38]刘睿,褚仁远.从视锥细胞到脑一色觉形成的神经回路[J].国际眼科纵览,2006,30(6):364-367.
    [39] Birch J, Chisholm IA, Kinnear P, Marre M, Pinckers AJLq Pokorny. Acquired color vision defects. In: Pokorny J, Smith VC. Congenital and Acquired Color Vision Defects. Albany, NY: Cmme& Stratton, 1979: 243-348.
    [40] Ikeda H, Wright MJ. Is amblyopia due to inappropriate stimulation of the sustained pathway during development? Br J Ophthalmol 1974, 58: 165-175.
    [41] Ciuffreda KJ, Levi DM, Selenow A. Amblyopia, Basic and Clinical Aspects. Boston: Butterworth-Heinemann, 1991: 348-350.
    [42] Nicholls JG Martin AR, Wallace BG, Fuchs PA. From Neuron to Brain 4th edition. Sunderland: Sinauer Associates, 2001.
    [43] Demirci H, Gezer A, Sezen F, Ovali T,Demiralp T, Isoglu-Alkoc U. Evaluation of the functions of the parvocellular and magnocellular pathways in strabismic amblyopia[J]. JPediatr Ophthalmol Strabismus 2002, 39(4): 215-21.
    [44] Previc FH. Functional specialization in the lower and upper visual fields in humans: Its ecological origins and neurophysiological implications[J]. Behav Brain Sci 1989, 13: 519-575.
    [45] Buckingham T, Watkins R Bans P, Bamfordz K. Hyperacuity thresholds for aloscillatory movement are abnormal in strabismic and anisometropic amblyopes[J]. Optom Vis Sci 1991, 68: 351-356.
    [46] Shapley R. Visual sensitivity and parallel retinocortical channels[J]. Ann Rev Psychol 1990, 41: 635-658.
    [47] Wiesel TN, Hubel DH. Receptive fields of cells in striate cortex of very young,visually inexperienced kittens[J]. Neurophysiol 1963, 26: 994- 1002.
    [48] Crewther SG. Neural site of strabismic arnblyopia in cats: X-cell acuities in the LGN[J]. Exp Brain Res, 1988, 72: 503-509.
    [49]阴正勤.单眼内斜幼猫空间分辨力发育的P-ERG和P-VEP分析[J].眼底病,1992,(2):65-71.
    [50]邵立功.弱视猫视系三级神及突触的超微结构研究[J].中华眼科杂志,1994,(1):53-56.
    [51] Chino YM, Shansky MS, Jankowski WL, Banser FA. Effects of rearing kittens with convergent strabismus on development of receptive-field properties in striate cortex neurons[J]. Neurophysiol, 1983, 50: 265.
    [52] Von Noorden GK, Middleditch PR. Histology of the monkey lateral geniculate nucleus after unilateral lid closure and experimental strabismus: further observations[J]. Invest Ophthalmol, 1975, 14: 674.
    [53] Ikede H. Amblyopic cells in the lateral geniculate nucleus in kittens raised with surgically produced squint[J]. Physiol, 1975, 256: 41-42.
    [54] Ikeda H. Is amblyopia due to inappropriate stimulation of sustained visual pathways during development[J]. Br J Ophthalmol, 197, 63: 243.
    [55] Ande rson SJ, Holliday IE, Harding GF. Assessment of cortical dysfunction in human strabismic amblyopia using magnetoencephalography[J]. Vis Res, 1999, 39(9): 1723- 1738.
    [56] Lowel S, Engelmann R. Neuroanatomical and neurophysiological consequences of strabismus: changes in the structural and functional organization of the primary visual cortex in cats with alternating fixation and strabismic amblyopia. Strabismus, 2002, 10(2): 95-105.
    [57]余敏忠.斜视性弱视眼的多焦视觉诱发电位特征[J].眼科新进展,2001,21(4):246- 248.
    [58]刘双珍,虞林丽,吴小影,闵晓珊.屈光不正性弱视患者视网膜厚度的变化[J].国际眼科,2006,6(2):384- 386.
    [59] Schroder JH, Fries P, Roelfsema PR, Singer W, Engel AK. Ocular dominance in extrastriate cortex of strabismic amblyopic cats[J]. Vis Res, 2002, 42(1): 29- 39.
    [60] WongAM, Burkhalter A, Tychsen L, Suppression ofmetabolic activity caused by infantile strabismus and strabismic amblyopia in striate visual cortex of macaque monkeys[J]. JAAPOS, 2005, 9(1): 37- 47.
    [61]史学锋,赵堪兴,刘虎,钱学翰.斜视性弱视猫视皮层突触活性改变[J].眼科研究,2004,22(5):497.
    [62] Crowley JC, Katz LC. Early deve1opment of ocular dominance columns[J]. Science, 2000, 290(5495): 1321-1324.
    [63] Smith EL 3rd, Chino YM, Ni J, Cheng H, Crawford ML, Harwerth RS. Residual binocular interaction in the striate cortex of monkeys reared with abnormal binocular vision[J]. Neurophysiol, 1997, 78(3): 1353-1362.
    [64] Yin ZQ, Deng ZM, Crewther SG, Crewther DP. Altered expression of alternatively spliced isoforms of the mRNA NMDARl receptor in the visual cortex of strabismic cats[J]. Molecular Vision , 200l, 20(7): 27l-276.
    [65] Catalano SM, Chang CK, Shatz CJ. Activity-dependent regulation of NMDAR1 immunoreactivity in the developing visual cortex[J]. Neurosci, l997, 17(21): 8376-8390.
    [66] Wong AM, Burkhalter A, Tychsen L. Neuroanatomic mechanism for suppression of the non-dominant eye in striate cortex of amblyopic/strabismic monkey: role of inhibitory horizontal connections[J]. Invest Ophthalmol Vis Sci, 2003, 44: 4826
    [67]孙庆艳,张长征,梅斌.猫年龄相关的视网膜γ-氨基丁酸和神经丝蛋白表达[J].解剖学杂志,200,28(5):570-574.
    [68] Levent hal AG, Wang Y, Pu M , et al . GABA and its agonists improved visual cortical function in senescent monkeys[J]. Science, 2003, 300 (5620): 7212722.
    [70] Sillito AM, Kemp JA. The influence of GABAergic inhibitory processes on the receptive field structure of X and Y cells in cat dorsal lateral geniculate nucleus[J]. Brain Res, 1983, 277: 63-77.
    [71] Mower GD, Christen WG. Evidence for an enhanced role of GABA inhibition in visual cortical ocular dominance of cats reared with abnormal monocular experience[J]. Brain Res Dev Rrain Res, 1989, 45(2): 211-218.
    [72] Hendry SH, Jones EG. Unilateral eyelid suture increases GABAA receptors in cat visual cortex[J]. Neuron, 1988, 1(8): 702-712.
    [73] ShawC, CynaderM. Unilateral eyelid suture increases GABAA receptors in cat visual cortex[J]. Brain Res 1988, 468(1): 148-153.
    [74] Hendry S, Carder RK. Organization and plasticity of GABA neurons and receptors in monkey visual cortex[J]. Prog Brain Res, 1992, 90: 477 -502.
    [75] Nie F, Wong-Riley MT. Metabolic and neurochemical plasticity ofgamma-aminobutyric acid-immunoreactive neurons in the adult macaque striate cortex following monocular impulse blockade: quantitative electron microscopic analysis[J].Comp Neurol, 1996; 370(3): 350-366.
    [76] Kemp JA, Sillito AM. The nature of the excitatory transmitter mediating X and Y cell inputs to the cat dorsal lateral eniculate nucleus[J]. Physiol Lond, 1982, 3(23): 377-391.
    [77] Hartveit E, Heggelund P. Neurotransmitter receptors mediating excitatory input to cells in the cat lateral geniculate nucleus: Nonlagged cells[J].Neurophsiol, 1990, 63: 1361-1372.
    [78] Heggelund P,Hartveit E.Neuro transmitterreceptors mediating excitatory input to cells in the cat lateral geniculate nucleus: Lagged cells[J]. Neurophysiol, 1990, 63: 1347-1360.
    [79] Rauschecker Egert U, Kossel A. Effects of NMDA antagonists on developmental plasticity in kitten visual cortex[J]. DevNeurosci 1990, 8: 425-435.
    [80]彭形.神经生长因子生物学效应的研究进展[J].检验医学与临床,2009,6(3):203-205.
    [81]邵立功.弱视模型视觉神经系统的神经生长因子表达特征研究[J].海军总医院学报,2006,19(4):212-217.
    [82] Domenici L,Berardi N, Carmignoto G, etal. Nerve growth factor prevents the amblyopic effects of monocular deprivation[J]. Proc Natl Acad Sci USA, 1991, 88: 8811-8815.
    [83] Giorgio C, Carmignoto G. Effects of nerve growth factor on neuronal plasticity of the kitten visual cortex[J]. Physiol, 1993, 464: 343-360.
    [84]邵立功,郭静秋.不同时限单眼斜视和剥夺猫视觉系统的神经生长因子表达研究[J].眼科,2000,9(3):181-186.
    [85] Vanessa Beijamini, Francisco Silveira Guimaraes.c-Fos expression increase in NADPH-diaphorase positive neurons after exposure to a live cat[J]. Behavioural Brain Research, 2006, 170: 52-61.
    [86] Sagar SM. Expression of c-fos protein in brain:metabolic mapping at the cellular level[J]. Science, 1988, 240: 1328-1331.
    [87] Estel Van der Gucht, Ann Massie, Bert De Klerck,etal. Molecular cloning and differential expression of the cat immediate early gene c-fos[J]. Molecular Brain Research, 2003, 111: 198-210.
    [88] Beaver CJ, Mitchell DE, Robertson HA. Immunohistochemical study of the pattern of rapid expression of c-fos protein in the visual cortex of dark-reared kittens following initial exposure to light[J]. J comp Neurology, 1993, 333: 469-484.
    [89] Estel Van der Gucht, Stefan Clerens, Sandy Jacobs, etal. Light-induced Fos expression in phosphate-activated glutaminase and neurofilament protein- immunoreactive neurons in cat primary visual cortex[J]. Brain Research, 2005, 1035: 60-66.
    [90] Reis RAM, VenturaALM, KubruslyRCC, etal. Dopaminergic signaling in the developing retina[J]. Brain Research Reviews, 2007; 54: 181-188.
    [91]周咏东,严密,张军军.可见光照对培养的人视网膜色素上皮细胞凋亡的影响[J].中华眼底病杂志,2002,18:227-300.
    [92] Tibber MS, Whitmore AV, Jeffery G. Cell division and cleavage orientation in the developing retina are regulated by L-DOPA[J]. J Comp Neurol, 2006, 96: 369-381.
    [93] Leguire, Walson PD, Roger GL, etal. Longitudinal study of levodopa/ carbidopa for childhood amblyopia[J]. Pediatr Ophthalmol Strabismus 1993, 30(6): 354-360.
    [94] Dadeya S, Vats P, Malik KP. Levodopa/carbidopa in the treatment of Amblyopia[J]. PediatrOphthalmol Strabismus, 2009, 46(2): 87-92.
    [95] Gottlob I, Stangler-Zuschrott E. Effect of levodopa on contrast sensitivity and scotomas in human amblyopia[J]. Invest Ophthalmol Vis Sci, 1990, 31: 776-780.
    [96]马丽卿,蟾素,方春庭.思利巴治疗儿童弱视的初步临床观察[J].斜视与小儿眼科杂志,2000,8(2):53-57.
    [97]谢梅芬,张映萍,谢铁强.思利巴联合传统综合疗法治疗年长儿童弱视疗效分析[J].中国斜视与小儿眼科杂志,2009,17(4):158-162.
    [98]林志洪.左旋多巴联合综合疗法治疗儿童弱视的疗效观察[J].国际医药卫生导报,2007,13(3):47-50.
    [99] Campos EC, Schiavi C, Benedetti P. Effect of citicoline on visual acuity in amblyopia:preliminary results[J]. Graefes Arch Clin Exp Ophthalmol, 1995, 233: 307-312.
    [100]韩冬,吴晋晖,闫飞虎.弱视治疗研究新进展[J].国际眼科杂志,2009,9(12):2382-2385.
    [101] Repka MX, Wallace DK, Beck RW, eta1.Two-year follo-up of a 6-month randomized trial of atropine vs patching for treanment of moderate amblyopia in children[J]. Arch Ophthalmol, 2005, 123(2): 149 -157.
    [102]陈秀兰,吕晓川,王晓蕾.复方樟柳碱注射液的稳定性研究[J].解放军药学学报,2000,16(2):76-79.
    [103]陆孟婷,陶永贤,李平华.复方樟柳碱联合物理疗法治疗弱视的临床观察[J]. 2009,31(19):1905-1907.
    [104]李谊,王自勤.复方樟柳碱治疗视神经挫伤25例[J].国际眼科杂志,2006,6(2):486-487.
    [105]周至安,欧扬,唐由之.参明汤治疗屈光不正性弱视疗效观察[J].中医眼科杂志,2003,13(4):219-220.
    [106]李迎舒,马红霞.益气聪明汤加减合耳穴贴压治疗儿童弱视86例总结[J].湖南中医杂志,2006,22(4):29-30.
    [107]闫钟蒲,郭英,李玲.综合疗法治疗儿童弱视74例[J].新中医,2006,38(4):78.
    [108]李振萍,邱波,王燕.增视灵口服液治疗儿童轻中度弱视35例[J].陕西中医,2006,27(10):1209-1210.
    [109]岳丽菁,黄玉有.明目地黄丸治疗大龄儿童弱视[J].眼科新进展,,2005,25(5):481-482.
    [110]毛淑敏,李承德,吕宁宁.自制增视灵丸治疗儿童远视弱视169例[J].中医药临床杂志,2005,17(4):370-372.
    [111]梁学政,吴西西.地黄明目颗粒的制备及临床应用[J].制剂技术,2006,14(6):54-55.
    [112]吴西西,代一权,谭建伟.中药治疗儿童弱视临床研究[J].中国中医眼科杂志,2003,13(3):134-136.
    [113]黄国林.弱视灵合后像疗法治疗儿童弱视.浙江中医杂志,1997,32(8):351-352.

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