病理性近视眼的研究进展

通过复习近年来相关文献,对近视眼发生发展机制与形觉剥夺之间的关系进行综合评述。认为近视眼的发生及眼轴延长与形觉剥夺有一定关系,深入研究其相关机制,对近视眼的早期防治具有重要意义。     

青少年近视眼防治研究进展

近年来，青少年近视眼发病率不断上升，成为日趋严重的社会问题，并成为新的研究热点。关于近视眼形成机制，新的形觉剥夺学说的提出对于传统的调节学说以及现有的近视眼防治工作提出了强有力的挑战。本文将根据近年有关文献，对常用的近视矫正与防治措施对于青少年近视进展的影响进行综述如下。     

一氧化氮与形觉剥夺性近视眼

一氧化氮是近年来发展的视网膜神经递质。一氧化氮合酶是合成一氧化氮的关键酶，在视网膜分布广泛。一氧化氮不仅参与了视觉信息的形成，整合和传导，具有重要的生理功能，而且在形觉剥夺实验性近视眼的发生中起重要作用。其作用机制尚不清楚，可能与一氧化氮抑制细胞增殖，调节巩膜基质中金属蛋白酶的活性，影响视网膜中其他生物活性物质的合成和释放密切相关。     

近视动物模型及发病机制的研究进展

近视已成为一种常见病,影响公众生活质量,危害公众健康,探索其发病机制有助于疾病的预防和治疗。然而目前近视的发病机制尚不明确,仍然是研究的重点和难点。自20世纪70年代发展至今,近视动物模型的相关研究已有突破性的进展,从分子机制、信号通路、药物干预等方面为近视发病机制的研究提供了证据和思路。本文就常见近视动物模型及发病机制的研究进展进行综述。     

形觉剥夺性和光学离焦性近视豚鼠视紫红质表达变化研究

目的：研究形觉剥夺性和光学离焦性近视豚鼠视紫红质的表达变化，探讨视紫红质表达与实验性近视眼之问的关系。方法：40只出生后1周的豚鼠随机分为形觉剥夺组和光学离焦组（n=20），形觉剥夺组单眼戴半透明（半透明薄膜贴于平镜表面）平光硬性角膜接触镜片（Rigid gass—permeable contactlens，RGP），光学离焦组单眼戴-4．0DRGP镜片，另一只眼为对照组。戴镜干预后1、2周各组分别测量屈光度、眼轴长度、玻璃体腔深度，并于上午10～12点钟取材，实时荧光定量PCR观察视紫红质mRNA的变化，Western—blot观察视紫红质的变化，进行对比比较，统计分析。结果：实验干预后1周，形觉剥夺组和光学离焦组与对照组相比各项指标无显著性差异（除形觉剥夺组屈光度以外）。实验干预后2周，与对照组相比较，形觉剥夺组和光学离焦组明显发生近视、眼轴延长、玻璃体腔加深（t：22．20、18．32、19．65、15．78、6．18、11．20，P〈0．01）；形觉剥夺组视紫红质及其mRNA表达均增加（t=17．489、14．31，P〈0．05），光学离焦组视紫红质及其mRNA表达无明显变化。结论：视紫红质的表达可能参与了形觉剥夺性近视眼的形成，而在光学离焦性近视眼中作用有限，     

豚鼠实验性近视眼巩膜的羟脯氨酸含量改变

目的通过豚鼠形觉剥夺性近视眼巩膜羟脯氨酸含量的检测,分析形觉剥夺对豚鼠巩膜不同区域胶原的影响,探讨胶原水平的变化在哺乳类动物近视眼发生机制中的作用.方法出生3周的断乳花色雄性豚鼠24只,单眼眼睑缝合75d后,检影,测眼轴.后极和前部巩膜分别称重后,以蛋白酶K消化和盐酸水解,氯胺T氧化比色法测每毫克巩膜中的羟脯氨酸含量.结果豚鼠75d的形觉剥夺诱导了约-9D的相对近视和0.39mm的眼轴延长.剥夺眼前部巩膜和后极巩膜的羟脯氨酸含量有显著性统计学差异(P＜0.001);对照眼前后巩膜的羟脯氨酸含量无统计学差异(P＞0.05);双眼前部巩膜的羟脯氨酸含量差异无统计学意义(P＞0.05);双眼后部巩膜的羟脯氨酸含量差异有显著性(P＜0.001).结论豚鼠形觉剥夺性近视眼时,主要是后极部羟脯氨酸含量减少,即后极部的巩膜胶原优先受影响.由于后极部巩膜胶原减少,减弱了巩膜的抵抗力,使眼轴易于延展而发生近视.     

实验性近视眼组织病理及超微结构观察

目的 研究2种不同诱导方法所致鸡近视眼组织病理改变,探索其发病机制。方法 雏鸡单眼遮盖或戴凹透镜,3周后验光及A超测定眼轴长,抽出眼球,行光镜及电镜检查。结果 透镜诱导眼和形觉剥夺眼产生相似的病理形态及超微结构改变,主要表现为后极部巩膜软骨层增厚,纤维层变薄。视杆细胞外节延长及视网膜色素上皮细胞胞质内吞噬体减少。结论 鸡眼对2种不同的视觉环境变化作出的反应是相似的。     

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。     

基质金属蛋白酶-2在实验性近视眼鸡巩膜成纤维细胞的表达

目的研究基质金属蛋白酶-2(matrix metalloproteinases-2,MMP-2)在形觉剥夺性近视眼(formdeprivation myopia,FDM)鸡巩膜成纤维细胞的表达。方法20只1d龄来亨雏鸡以半透明眼罩遮盖右眼14d制备FDM动物模型,随机取10只FDM眼去除遮盖7d作为恢复组,均以对侧未遮盖眼作为对照组。将各组小鸡眼后极部巩膜成纤维细胞作体外培养并传2代,行光镜与透射电镜形态学观察,并采用SABC免疫细胞化学染色法检测MMP-2的表达,进行计算机图像分析及统计学检验。结果培养的正常鸡巩膜成纤维细胞胞浆表达MMP-2,阳性灰度值为192·2319±1·2521。FDM组细胞MMP-2染色阳性灰度值为168·1730±5·0039,较对照组MMP-2表达明显增高(P<0·01)。恢复组阳性灰度值为180·4001±2·3522,其MMP-2表达较FDM组有所回降(P<0·01),但与对照组相比仍有升高,差异有显著性(P<0·01)。结论MMP-2参与形觉剥夺性近视眼的发生发展与恢复的过程,在近视发生机制中起重要作用。     

豚鼠短期形觉剥夺性近视屈光度眼轴及巩膜改变

目的:观察豚鼠短期形觉剥夺性近视(form deprivationmyopia,FDM)眼轴、屈光度变化及后极部巩膜病理性改变。方法:4周龄健康豚鼠40只,随机分成形觉剥夺实验组和年龄匹配正常对照组各20只。形觉剥夺实验组分为剥夺1,4,7和14d4个亚组,右眼为剥夺眼,采用半透明眼罩遮盖诱导轴性近视,左眼不予处理。对剥夺前后实验组和对照组双眼屈光度、眼轴进行测量,并对后极部巩膜进行HE染色光镜观察和透射电镜观察。结果:形觉剥夺7d近视程度和眼轴长度改变迅速,之后减慢并趋于平稳。4个实验亚组剥夺眼与实验前比较相对近视-0.30±0.45D,-3.65±0.78D,-6.98±0.65D,-8.68±1.12D,相对眼轴延长4.8±3.2,129.0±12.6,159.0±10.1,184.4±10.4μm。其中4,7,14d实验亚组剥夺眼与对照眼差别有统计学差异(P<0.01),剥夺眼后极部巩膜明显变薄,成纤维细胞密度降低,细胞外基质增多。1,4,7,14d实验亚组形觉剥夺眼后极部巩膜胶原纤维平均直径102.0,67.4,52.2,49.8nm,与正常对照眼比较差别有统计学意义(P<0.05)。结论:4周龄豚鼠单眼形觉剥夺4d即可出现轴性近视,1d即有巩膜病理改变,形态学改变先于生物学改变,形觉剥夺7d为近视发展高峰期。     

Axial myopia induced by a monocularly-deprived facemask in guinea pigs: A non-invasive and effective model

This study evaluated the efficacy of a facemask, a non-invasive and potentially more reliable method, in inducing axial myopia in guinea pigs. Thirty-six animals were randomly assigned to 3 groups: MDF (monocularly-deprived facemask, n=6), lid-suture (eyelids sutured monocularly, n=24) and normal control (free of form deprivation, n=6). All the groups underwent biometric measurement (refraction, corneal curvature and axial length) prior to the experiment. All animals in the MDF group underwent biometric measurement at each of the 4 timepoints (2, 4, 6 and 8 weeks of form deprivation). In the lid-sutured group, the animals were randomly assigned to 4 subgroups (n=6 each) and each subgroup underwent biometric measurement at one of the timepoints matching those of the MDF group. In the normal control group, all animals underwent biometric measurement at each of the timepoints matching those of the 2 experimental groups. Placement of a facemask on an animal took approximately 10 sec and all the facemasks remained in place at all timepoints. The procedure of lid-suture took at least 20 min for an animal and rupture of the sutures occurred in 50% of the animals after 4 weeks. The MDF eyes developed myopia from −2.21±2.11D (Mean±s.d.) at 2 weeks to −4.38±2.14 at 8 weeks (p<0.05 at all timepoints, compared to the contralateral eyes) with a lengthening of the vitreous chamber from 0.17±0.05 mm at 2 weeks to 0.29±0.12 mm at 8 weeks (p<0.01 at all timepoints, compared to the contralateral eyes). The lid-sutured eyes developed myopia from −2.38±1.21D at 2 weeks to −4.75±1.39D at 8 weeks (p<0.05 at all timepoints, compared to the contralateral eyes) with a lengthening of the vitreous chamber from 0.13±0.02 mm at 2 weeks to 0.30±0.10 mm at 8 weeks (p<0.05 at 2, 4, 8 weeks, but >0.05 at 6 weeks, compared to the contralateral eyes) and an increase in the radius of the corneal curvature (0.20±0.07 mm at 4 weeks, p<0.01; 0.17±0.05 mm at 8 weeks, p<0.05; compared to the contralateral eyes). Both the MDF and lid-sutured groups had a similar development in myopia and vitreous length (MDF vs lid-suturing: p>0.05 at all timepoints, one-way ANOVA with Bonferroni correction). This development was significantly faster than in the normal control group (MDF or lid-suture vs normal control: p<0.05 to <0.01 from 2 to 8 weeks, one-way ANOVA with Bonferroni correction). The radius of corneal curvature in the lid-sutured group was significantly greater than in either the MDF group or the normal control group since 4 weeks of form deprivation (p<0.05, one-way ANOVA with Bonferroni correction). Treatment with MDFs is as effective as the lid-suture in inducing axial myopia in guinea pigs. This method is non-invasive and allows evaluation of the same group of animals at different timepoints so that the number of animals required could be minimized without affecting the accuracy of the results.     

多巴胺对兔实验性形觉剥夺性近视形成的影响

目的:研究多巴胺对实验性近视形成的影响。方法：7日龄幼兔52只,分A,B,C3组。A组20只,单纯缝合眼睑;B组16只,缝合眼睑＋玻璃体内注射多巴胺;C组16只,缝合眼睑＋玻璃体注射生理盐水。结果：A,C两组中两眼玻璃体腔长度、眼轴长度和玻璃体腔长度／眼轴长度间均有非常显著的统计学差异（P＜0.001）,前房深度和晶状体厚度无统计学差异。巩膜胶原纤维A,C两组中明显变细,而在B组中改变较轻。结论：形觉剥夺能导致眼球的轴性延长,玻璃体腔延长和VCL／AL增大是其形态学原因,巩膜纤维的变细、延长是其病理学原因之一,而多巴胺能部分阻止这些改变。     

国产bFGF在鸡形觉剥夺性近视形成中的作用

目的 建立形觉剥夺性近视模型。观察碱性成纤维细胞生长因子（bFGF)对近视发生的抑制作用。方法 出生后第2天的小鸡应用半透明塑 料眼罩行右眼单眼遮盖,随机分成4组,每组8只鸡,其中3组遮盖眼分别结膜下注射bFGF、阿托品和bFGF联合用药、阿托品。单纯遮盖组（MD）不作任何治疗。14天后测定结果,并衡量药物疗效。结果 单纯遮盖组眼与阿托品组（AI）、联合用药组（Abl)的遮盖眼相比眼球明显增大,而与bFGF组相比仅略有增大,阿托品组及联合用药组治疗眼的屈光度、眼轴长度、赤道径麦收单纯遮盖眼相比均有显著性差异。而bFGF组与单纯遮盖眼相比没有显著性差异。阿托品组及联合用药组与bFGF组相比有显著性差异。结论 早期形觉剥夺可导致近视的形成,阿托品可以完全抑制形觉剥夺性近视的发生,而bFGF抑制近视形成的作用甚微。     

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。     

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。     

A retrospective study: form-deprivation myopia in unilateral congenital ptosis

Background: The aim of this retrospective study was to investigate the relationship between unilateral congenital ptosis in patients older than eight years and their refractive state and spherical equivalent refraction (SER). Methods: The study involved a review of the clinical records of 85 patients admitted to the First Affiliated Hospital, Sun Yat‐sen University between 1998 and 2010 with unilateral congenital ptosis. The average age was 16.83 years (nine to 27 years). The patients were classified into mild (27 cases), moderate (37 cases) or severe (21 cases) ptosis according to the degree of the droopy eyelid covering the cornea. The fellow eyes served as controls. Results: In 85 eyes with unilateral ptosis, the frequency of myopia (SER of ‐0.50 D or more myopia) was significantly higher than in the fellow eye (47 versus 32, p = 0.031). The frequency of myopia in eyes with severe unilateral ptosis was significantly higher than in the fellow eyes (16 versus 7, p = 0.012), whereas there were no significant differences in patients with mild (15/27 versus 13/27, p = 0.79) or moderate (16/37 versus 12/37, p = 0.47) unilateral ptosis. Similarly, the SER was significantly more myopic in eyes with severe ptosis compared with the fellow eye (‐1.37 D versus ‐0.85 D, p = 0.01), whereas no significant differences were found in patients with mild or moderate unilateral ptosis. Conclusions: The results showed a higher frequency of myopia and more myopic SER in eyes with severe unilateral ptosis compared with the fellow eye. The myopia found in eyes with unilateral ptosis might be caused by a mechanism similar to that resulting in myopia among animals subjected to form deprivation. It is important to pay attention to possible refractive error in patients with unilateral ptosis. Surgical correction of unilateral ptosis at an early age is recommended.