形觉剥夺性眼病与轴性近视关系的探讨

目的　研究形觉剥夺对眼球发育及屈光状态的影响 ,探讨近视眼发病机理及近视发生的危险因素。方法　对一组单眼患早期形觉剥夺性眼病患者的眼球各屈光因子 ,进行生物学测量比较 ,确定其屈光状态 ,并用t检验及多元相关分析的方法找出形觉剥夺性近视的危害因子。结果　患眼与健眼相比 ,患眼有较明显的近视倾向 ,平均屈光力相差 1 2 0 1D。两组比较角膜屈光力、晶状体厚度差异无显著性意义 ;前房深度、玻璃体腔长度、眼轴长度、眼的屈光状态差异均具有显著性意义。玻璃体腔长度为近视眼发生的主要危险因素。结论　早期形觉剥夺可发生近视眼 ,其主要危险因子是眼轴长度 ,主要危害部位在眼后段。尽早去除形觉剥夺 ,保持或恢复视觉发育敏感期的正常视觉环境 ,有利于预防近视眼的发生。     

实验性形觉剥夺性近视研究的进展

随着实验性近视眼模型研究的发展,对其形成机制的探讨取得一定成果。近年,尤其对形觉剥夺性近视及其形成机制的研究引起了人们极大的兴趣,因为其与人类近视有很多相似之处。本综述就实验性形觉剥夺性近视的诱导方法、不同诱导方法的相应机制、不同物种的动物诱导性近视的异同、及有关形觉剥觉性近视形成中的视网膜、脉络膜及巩膜的作用作一综合阐述,从而对形觉剥夺性近视从诱导方式到其发生机制有一综合认识。     

实验性形觉剥夺性近视研究的进展

随着实验性近视眼模型研究的发展，对其形成机制的探讨取得一定成果。近年，尤其对形觉剥夺性近视及其形成机制的研究引起了人们极大的兴趣，因为其与人类近视有很多相似之处。本综述就实验性形觉剥夺性近视的诱导方法、不同诱导方法的相应机制、不同物种的动物诱导性近视的异同、及有关形觉剥觉性近视形成中的视网膜、脉络膜及巩膜的作用作一综合阐述，从而对形觉剥夺性近视从诱导方式到其发生机制有一综合认识。     

形觉剥夺性近视中巩膜变化的生物学机制

近视眼的发病机制不明，形觉剥夺可以诱导典型的近视动物模型，形成形觉剥夺性近视眼(form—deprivationmyopia，FDM)。通过细胞和分子水平的研究发现，FDM的变化主要表现在眼球局部，形觉剥夺可诱导巩膜软骨细胞增殖，细胞外基质(extracellularmaterial，ECM)基因表达异常，ECM增加，巩膜胶原纤维改变等引起巩膜重塑，导致眼轴延长，近视屈光度增加。本文就FDM巩膜变化生物学机制的研究进展作一综述。     

豚鼠形觉剥夺超高度近视模型的形态学研究

目的建立豚鼠形觉剥夺超高度近视模型并观察其后极部各层组织的病理组织学变化。方法 2周龄三色豚鼠分为形觉剥夺组（12只）和非形觉剥夺对照组（8只）,于形觉剥夺前,形觉剥夺后4、6、10、14周分别对各组进行检影和眼轴性参数测量。通过病理组织学光镜检查分析形觉剥夺14周后各组视网膜、脉络膜和巩膜厚度及其形态学的变化。结果豚鼠形觉剥夺后随时间延长近视度数逐渐增高,10周后可达-10.00 D以上的超高度近视,14周后近视度数更高、个别个体可达-20.00 D。眼轴性参数相应延长。形觉剥夺超高度近视眼视网膜、脉络膜和巩膜较对照组均明显变薄并有病理性改变。结论应用遮盖法对豚鼠施行长期单眼形觉剥夺会形成超高度近视,10周后可达-10.00 D以上,超高度近视眼巩膜、脉络膜和视网膜明显变薄,脉络膜和巩膜结构发生紊乱。视网膜结构中感光细胞层变薄最为明显,推测其对超高度近视的发生起重要作用。     

形觉剥夺近视眼巩膜的超微结构观察

本文采用形觉剥夺方法，在海赛克鸡雏眼建立近视眼动物模型，探索形觉剥夺近视眼赤道部巩膜组织的超微结构变化。结果发现，实验组巩膜软骨细胞线粒体及粗面内质网丰富，并可见数量较多的溶酶体，在溶酶体内出现空白区和大空泡，双核细胞增多。提示形觉剥夺是近视眼产生的重要原因。     

豚鼠形觉剥夺性近视眼巩膜基质金属蛋白酶-2表达的实验研究

目的观察形觉剥夺性近视眼后极部巩膜组织细胞外基质的改变以及基质金属蛋白酶-2(matrix melallopro-teniases,MMP-2)表达的变化,以揭示其与形觉剥夺性近视眼后极部巩膜组织改变的关系。方法采用形觉剥夺方法建立豚鼠的近视动物模型。分别测量后极部巩膜组织厚度和干重,应用免疫组化技术研究MMP-2在形觉剥夺8周后的豚鼠处理眼与对照眼后极部巩膜中表达的差异。结果形觉剥夺后处理眼较对侧眼及正常对照眼有明显近视形成(P<0.001),形成的近视度数分别为(-8.20±1.21)DS和(-7.00±1.03)DS;剥夺后后极部巩膜厚度明显变薄(P<0.01),剥夺前后厚度差为(13.8±8.2)μm;干重减轻(P<0.05),剥夺前后干重差为(0.13±0.07)mg。MMP-2在形觉剥夺后的豚鼠处理眼、对侧眼及正常对照眼后极部巩膜的表达定位于成纤维细胞胞浆和细胞外基质中。处理眼后极部巩膜中MMP-2表达量明显高于对侧眼及正常对照眼(P<0.001)。结论形觉剥夺眼后极部巩膜组织细胞外基质有显著降解趋势,同时MMP-2表达升高。MMP-2可能参与了形觉剥夺性近视发生过程中巩膜的重塑。     

纤维连接蛋白在形觉剥夺眼和正常眼的差异表达

目的：探讨实验性形觉剥夺性近视眼眼轴增大的影响因素,探讨导致形觉剥夺性近视眼的巩膜改变的分子水平机制。方法：单眼遮盖20只鸡雏4周制备实验性近视模型,然后使用免疫组织化学方法检测遮盖眼和对照眼的巩膜软骨组织的纤维连接蛋白（FN）表达情况。结果：遮盖眼巩膜软骨的软骨细胞质、细胞膜和软骨囊的FN的表达水平比对照眼明显增高（P＜0.01)。结论：FN与实验性近视眼的近视形成机制有关,可能有调节眼球增大的作用。     

离焦性近视发病机制的研究进展

近视眼发生的机制尚未完全明了.离焦性近视与人类近视眼有较多相似之处,其生理机制与人类近视原型更接近,因此对离焦性近视发病机制的研究将有助于对人类近视眼的认识.目前关于离焦性近视发病机制方面的研究已取得一些进展,揭示了其与形觉剥夺性近视的异同,形态学及超微结构的改变,调节因素、局部视网膜机制、视网膜神经介质、基因表达在其发病机制中的作用等.     

豚鼠形觉剥夺性近视视网膜早基因c-fos与酪氨酸羟化酶关系的研究

形觉剥夺性近视（FDM）动物模型研究表明，高度近视眼形成主要由于局部视网膜的视觉信息可调控巩膜的生长反应，但目前对其具体发生机制不清。我们通过对豚鼠FDM形成及恢复过程中视网膜早基因c-fos和酪氨酸羟化酶（TH）的动态变化及相关关系进行研究，以探讨c-fos和TH在豚鼠FDM视网膜信号转导的可能分子机制。[第一段]     

Form deprivation myopia in mature common marmosets (Callithrix jacchus)

PURPOSE: Experimental manipulations of visual experience are known to affect the growth of the eye and the development of refractive state in a variety of species including human and nonhuman primates. For example, it is well established that visual form deprivation causes elongation of the eye and myopia. The effects of such manipulations have generally been examined in neonatal or juvenile animals. Whether adolescent common marmosets (a new world primate) are susceptible to form deprivation myopia was studied. METHODS: Five adolescent marmosets were used in this study. Monocular form deprivation was induced by lid closure for 12 to 20 weeks, starting between 299 and 315 days of age. The effects of deprivation were assessed with keratometry, A-scan ultrasonography, and cycloplegic refractions. Both eyes (treated and fellow control) were measured before lid-closure, at the end of the deprivation period, and several times over the following 8 to 12 weeks. RESULTS: Adolescent marmosets are susceptible to visual form deprivation myopia. The experimental eyes showed significant axial elongation and myopia relative to the fellow control eyes. These changes were smaller, however, than those observed in younger eyes deprived for comparable periods. Like juvenile animals, the adolescent marmosets did not show recovery from myopia over the period monitored. CONCLUSIONS: The period for susceptibility to form deprivation myopia in the marmoset monkey extends beyond the early developmental period when ocular growth is rapid and emmetropization normally takes place. Visual form deprivation in adolescent marmosets with adult-sized eyes results in increased ocular growth and myopia. These data suggest that visual factors may influence the growth and refractive development of the human eye after puberty and may be involved in late-onset myopia.     

多巴胺在形觉剥夺性近视中作用的研究进展

近视作为一种全球发病率最高的屈光不正,其趋势日益增加,已成为眼科研究领域的热点。形觉剥夺性近视是实验性近视中较为成熟的造模方法。众多研究报道多巴胺作为一种调控视网膜及眼球生长微环境的神经递质,通过与多巴胺受体、途径间的相互作用,在形觉剥夺性近视的形成和抑制过程中具有重要意义。现就多巴胺对形觉剥夺性近视的影响及其生化机制进行探讨,以期为近视的实验研究提供参考。     

The response to visual form deprivation differs with age in marmosets

PURPOSE: To characterize the effects of visual form deprivation by diffuser in marmoset monkey eyes across a range of ages. METHODS: Twenty-four common marmosets were grouped by onset of deprivation (group 1: 0-39 days, n = 6; group 2: 40-99 days, n = 10; and group 3: 100-200 days, n = 8). Monocular form deprivation was induced with a white translucent diffuser worn for 28 to 88 days (mean durations: group 1, 32 days; group 2, 56 days; and group 3, 51 days). Refractive state, corneal curvature, and vitreous chamber depth were measured after cycloplegia. Both experimental and control eyes were measured multiple times before, during, and after the visual deprivation period. RESULTS: Marmosets in all age groups tested were susceptible to visual form deprivation myopia; however, the response to form deprivation was variable and included a majority with axial myopia (n = 15), several nonresponders (n = 4), a single late responder (axial myopia after the end of deprivation period), and several axial hyperopes (n = 4). For all animals that responded with axial myopia, the increase in vitreous chamber depth and myopia was inversely proportional to the age of onset of deprivation (ANOVA, P < 0.05). After the end of the period of deprivation, recovery from myopia by reduction of the axial growth rate was observed in three animals from group 1 and three animals from group 2. CONCLUSIONS: Form deprivation by diffusers disrupted emmetropization in marmosets over a range of ages. The responses varied among individuals and with age, suggesting that the maturity of the eye may influence the response to visual signals responsible for form deprivation myopia and perhaps emmetropization. Recovery from diffuser-induced form deprivation myopia was apparent in some animals, in contrast to that reported for visual deprivation by lid-suturing, and appears more prevalent in the younger animals.     

形觉剥夺在儿童近视中的表达

目的:通过调查处于生长发育期的儿童由于各种原因的形觉剥夺会否造成双眼在近视发生、发展中的不一致,从临床层面上证实形觉剥夺性近视,揭示近视发病的环境因素和机制,从而采取有效措施进行防治。方法:抽取门诊近视患儿114例,均常规行视力、眼位、主导眼、眼底、裂隙灯、规范的散瞳检影等检查,并通过问诊了解家族史及是否存在剥夺因素。比较双眼的视力、屈光度,并就形觉剥夺眼与屈光度的高低进行相关性统计分析。结果:双眼视力(P=0.000)及屈光度(P=0.006)均存在显著性差异,即形觉剥夺眼与双眼屈光度高者相关(P=0.005)。结论:处于生长发育期的儿童由于各种原因的单眼形觉剥夺可以造成双眼近视发生不一致,剥夺眼近视发生早,屈光度高。应引起重视并积极采取有效措施进行早期干预。     

Effects of prostaglandins on form deprivation myopia in the chick

PURPOSE: To investigate the possible role of endogenous prostaglandins in the development of form deprivation myopia, as well as the effects of exogenous prostaglandins using atropine as a positive control. METHODS: Monocular form deprivation was accomplished by mounting a translucent occluder on one eye of 2-3 day old chicks for 1-4 weeks. Ocular occlusion for 1-2 weeks was used for pharmacological blocking experiments. The axial length of the eye was measured by ultrasonography. RESULTS: Indomethacin, administered intramuscularly, subconjunctivally or intravitreally had no significant effect on myopia development. Exogenous PGE2, PGF2alpha and latanoprost acid administered subconjunctivally, or topically as isopropyl ester eyedrops had no statistically significant effect on the myopia development. However, PGF2alpha significantly (p<0.01) attenuated the development of myopia after intravitreal injection. The other two prostaglandins had no statistically significant effect. CONCLUSIONS: Endogenous prostaglandins are unlikely to play a significant role in the development of form deprivation myopia in the chick. However, PGF2alpha suprisingly seems to retard the development of form deprivation myopia, but only when administered intravitreally. Whether the mechanism of the myopia retardation is direct or indirect remains unknown.     

Refractive Changes in Chicks with Form-deprivation Myopia

Purpose: To study the refractive changes of form deprivation of myopia. Methods: Haisaik chickens were used to establish the animal models of myopia. Monocular eyelids were sutured for form deprivation on the 5th day after chickens birth. The chickens were examined by optometer and the anteroposterior axis, transverse and vertical diameters were measured by verniermicrometer. Results: Form deprivation leads to myopic refractive abnormality (P<0. 001). The ocular anteroposterior axis (P<0. 005), transverse and vertical diameters lengthen (P<0. 05).Conclusion: Form deprivation is the main cause of the development of myopia. Eye Science 1996; 12:138-139.     

Pirenzepine prevents form deprivation myopia in a dose dependent manner

Previous studies have demonstrated that muscarinic antagonists, such as atropine and pirenzepine, block form deprivation myopia in avian and mammalian models. The aim of the present investigation was to establish dose–response curves for intravitreal and subconjunctivally injected pirenzepine and to determine receptor specificity. Chicks were monocularly deprived of form vision for five days and received daily injections of either pirenzepine or saline. Keratometry, retinoscopy and A-scan ultrasonography of axial ocular dimensions were then taken. Intravitreally injected pirenzepine was effective at preventing form deprivation myopia in a dose dependent manner with an ED₅₀ of 175 μg. A 500 μg dose totally prevented induced myopia (+0.9 D versus −13.7 D) and axial enlargement (−0.14 mm versus +0.32 mm). Daily subconjunctival injection of pirenzepine was significantly less effective in preventing form deprivation myopia. Form deprivation myopia could still be induced in animals which had undergone pirenzepine treatment. Pirenzepine was effective in preventing the axial elongation associated with experimental myopia in a dose dependent manner and via a functional not toxic mechanism.     

视黄酸在早期形觉剥夺性近视豚鼠后巩膜中的变化

目的检测豚鼠早期形觉剥夺性近视（FDM）眼巩膜中视黄酸（RA）的水平,探讨RA在FDM眼后极部巩膜中的作用。方法3周龄三色豚鼠30只随机分组,正常对照组6只,形觉剥夺15d组和形觉剥夺24d组各12只,左眼用气球头套分别遮盖15d和24d,右眼为自身对照。实验前后均测量屈光度,实验结束后摘除眼球,测量眼轴长,应用高效液相色谱法（HPLC）测定后极部巩膜RA含量。结果形觉剥夺15d组、形觉剥夺24d组动物实验眼诱导出明显的相对近视,且与正常组比较差异有统计学意义（F=23.053,P〈0.05）。形觉剥夺15d组、形觉剥夺24d组实验眼眼轴均长于自身对照眼（P〈0.05）。形觉剥夺15d组、形觉剥夺24d组实验眼巩膜中RA水平较自身对照眼均明显升高（P〈0.01）,但形觉剥夺15d组、形觉剥夺24d组间比较差异无统计学意义（P=0.857）。结论形觉剥夺可诱导近视,且近视程度在早期随时间递增,形觉剥夺眼眼轴增长。豚鼠早期形觉剥夺眼后极部巩膜RA含量增多,但在15～24d时段内差异无统计学意义。     

形觉剥夺性近视中巩膜重塑机制的研究

近视是全球发病率最高的屈光不正,发病机制至今不明。形觉剥夺性近视（FDM）动物模型的建立为近视的病因学研究开辟了新局面。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。外界刺激作用于视网膜,启动视网膜一视网膜色素上皮层一脉络膜信号转导系统,把局部视网膜信号转化为调控巩膜重塑的信号,诱导细胞外基质异常表达,巩膜胶原纤维改变等,引起巩膜重塑。就FDM中不同种属动物间巩膜重塑发生的形态学变化及相关因素等做一综述。     

年龄对豚鼠形觉剥夺的敏感性及形觉剥夺性近视恢复能力的影响

目的 本试验通过对已性成熟的豚鼠进行形觉剥夺,以探求性成熟后年龄对豚鼠形觉剥夺敏感性以及形觉剥夺性近视恢复能力的影响.方法 实验研究.采用39只豚鼠,根据年龄分为3组,分别为9周组(18只),12周组(10只)和15周组(11只).所有动物在实验前测量双眼屈光状态后采用特制乳胶头罩随机遮盖1只眼,遮盖时间为3周.3周后,移除乳胶头罩,并在移除当天,移除后2d及7 d分别测量双眼的屈光状态.结果 经过形觉剥夺,9周组、12周组、15周组实验眼相对于对侧眼的近视最分别为(-2.53±1.89)、(-1.43±1.57)、(-0.60±1.48)D.3组动物的形觉剥夺眼与对侧眼屈光度数差异均有统计学意义(t=-5.691,-2.203,-2.760;P<0.05).在近视的形成量方面,9周组和15周组分别为(-2.53±1.89)D和(-0.60±1.48)D,差异有统计学意义(F=2.823,P<0.05).随着豚鼠年龄的增大,形觉剥夺所形成的近视量随之降低.在恢复期,仅9周组动物表现出实验性近视逐渐恢复的趋势,但差异无统计学意义,其余组动物均不出现明显近视恢复.结论 豚鼠在性成熟后依然对形觉剥夺敏感,但对形觉剥夺的敏感性随年龄的增大逐渐下降.性成熟后豚鼠短期内近视恢复(1周)能力已基本消失.敏感性和恢复能力的下降并不同步,两者与年龄的关系表现出不同的模式.