哌仑西平对豚鼠离焦性近视的作用及机制

目的 评价眼表应用M1受体桔抗剂哌仑西平对豚鼠离焦性近视(lens-induced myopia,LIM)的作用,并探讨其作用机制.方法 健康2周龄雄性豚鼠40只,随机分为4组:单纯遮盖组(Ⅰ组)、氯化钠组(Ⅱ组)、哌仑西平组(Ⅲ组)、正常对照组(Ⅳ组),各组各10只.Ⅰ组、Ⅱ组、Ⅲ组豚鼠均右眼配戴-10.0 D透镜,左眼开放;Ⅳ组豚鼠双眼不做任何处理.Ⅱ、Ⅲ组豚鼠的右眼每天2次分别滴生理盐水溶液和30 g·L-1复方哌仑西平眼液.4周后检测4组豚鼠双眼屈光度、眼轴长度,免疫组织化学法检测豚鼠视网膜多巴胺转运蛋白(dopamine transporter,DAT)表达情况.结果 4周后,4组实验眼屈光度、眼轴长度、视网膜DAT阳性细胞个数分别为:Ⅳ组(0.40±1.05)D、(7.64±0.18)mm、(37.00 ±3.48)个,Ⅲ组(-2.15±1.02)D、(7.66±0.03)mm、(35.60±3.74)个,Ⅰ组(-4.70 ±0.39)D、(8.02±0.17)mm、(24.20 ±3.73)个,Ⅱ组(-4.05 ±0.75)D、(7.86 ±0.19)mm、(23.40±2.77)个,与Ⅲ和Ⅳ组相比,Ⅰ和Ⅱ组实验眼形成中高度近视、眼轴明显延长、视网膜DAT阳性表达也低,差异均有统计学意义(均为P<0.05);Ⅲ组与Ⅳ组相比,各项检测指标差异均无统计学意义(均为P>0.05).结论 哌仑西平滴眼液能有效抑制豚鼠LIM的发展,能阻止LIM眼视网膜DAT表达水平的下降.     

外伤性视网膜脱离视网膜色素上皮细胞钙粘素表达变化

目的探究外伤性玻璃体积血视网膜脱离模型视网膜色素上皮细胞（RPE）细胞膜表面钙粘素（Cadherin）表达变化规律。方法90只健康有色兔，分为5组：Ⅰ组，外伤性玻璃体积血伴视网膜脱离组；Ⅱ组，孔源性视网膜脱离组；Ⅲ组，单纯视网膜裂孔组；Ⅳ组，玻璃体切除组；Ⅴ组，空白对照组。分别于手术后1、3、5、7、14、21、30d摘取眼球，酶消化和机械分离法分离RPE细胞，制成细胞悬液，用流式细胞仪检测RPE细胞膜上钙粘素表达水平。方差分析比较各组差异。结果各模型组RPE细胞钙粘素表达差异具有统计学意义（F=9．612；P〈0．001），Ⅰ组和Ⅱ组中RPE细胞钙粘素的表达水平明显低于Ⅲ组、Ⅳ组和Ⅴ组。不同时间点组中钙粘素表达差异具有统计学意义（F=7．95，P〈0．001）。Ⅰ组和Ⅱ组模型RPE细胞钙粘素表达均数无明显差异，与Ⅲ组、Ⅳ组和Ⅴ组比较差异显著。结论外伤性玻璃体积血伴视网膜脱离和孔源性视网膜脱离模型RPE细胞钙粘素表达在发病早期表达减弱，随着病情的发展钙粘素表达逐步恢复至正常。     

不伴明显视力下降的糖尿病视网膜病变患者黄斑部形态和功能检测

目的:探讨不伴明显视力下降的糖尿病视网膜病变(Diabetic retinopathy,DR)患者黄斑部形态和功能的改变.方法:对DR 0期组(未发现DR改变)、Ⅰ～Ⅱ期组及Ⅲ～Ⅳ期组患者进行光学相干断层扫描(Optical coherence tomography,OCT)及多焦视网膜电图(Multifocal electroreti-nography,mfERG)检查,并与同年龄组正常人相比较.结果:OCT检查确定DR Ⅰ～Ⅱ期组有3眼(10.0%)及DRⅢ～Ⅳ期组有6眼(23.1%)存在黄斑水肿.DRⅢ～Ⅳ期组各方位神经上皮层厚度比相应方位的正常组及DR 0期组增加(P＜0.05).同正常对照组相比,mfERG检查发现DR0期组、DR Ⅰ～Ⅱ期、DR Ⅲ～Ⅳ期组P1、N1波振幅下降,反应密度下降,差异有显著性(P＜0.05);但P1、N1波潜伏期未见延迟(P＞0.05).同DR Ⅰ～Ⅱ期组相比,DRⅢ～Ⅳ期组P1波及N1波潜伏期轻度延长、振幅下降、平均反应密度降低(P＜0.05).结论:视力无明显下降的DR患者中,随病情的加重,无论形态和功能上均已有异常,功能异常早于形态异常.     

不同条件体外培养的视网膜组织中NO及其合成酶变化

目的 :观察不同成份的培养液对成年犬视网膜组织进行体外培养的前后NO及其合成酶的改变 ,旨在为视网膜移植提供抗氧化能力的保护性方法。方法 :健康成年家犬 3 7只 (74眼 ) ,将动物随机分成六组 ,Ⅰ (新鲜视网膜组 )Ⅱ (常规培养液组 )Ⅲ (高浓度OCE组 )Ⅳ(低浓度OCE组 )Ⅴ (高浓度全脑组织提取液组 )Ⅵ (低浓度全脑组织提取液组 )培养一周。六组视网膜组织匀浆 ,离心 ,取上清液后进行NO、NOS生化指标的测定。结果 :Ⅰ～Ⅵ组视网膜组织NO、NOS含量差异有显著性。与Ⅰ组相比 ,Ⅱ、Ⅲ、Ⅴ、Ⅵ组NO、NOS值显著增高 ;与Ⅱ组相比Ⅲ、Ⅳ组NO、NOS值显著降低 ;且Ⅳ组与Ⅰ组NO值无统计学差异。Ⅳ组与Ⅲ组比较 ,NOS值降低明显。结论 :成年犬OCE中含有清除自由基、增强抗氧化能力的特殊物质。并且低浓度OCE较高浓度OCE对体外培养的视网膜组织抵抗NO的能力显著。     

不同病变时期Best卵黄样黄斑营养不良的光相干断层扫描图像特征

[目的]观察不同病变时期Best卵黄样黄斑营养不良(BVMD)的光相干断层扫描(OCT)图像特征.[方法]临床确诊为BVMD的28例患者56只眼纳入研究.所有患者常规行最佳矫正视力、裂隙灯显微镜、直接检眼镜、前置镜、眼底照相、眼电图、荧光素眼底血管造影检查.56只眼中,0期8只眼,Ⅰ期2只眼,Ⅱ期10只眼,Ⅱa期12只眼,Ⅲ期6只眼,Ⅳa期6只眼,Ⅳb期5只眼,Ⅳc期7只眼.患者同时行OCT检查,观察不同病变时期的OCT图像特征.[结果]OCT检查发现,0期患眼黄斑区未见明显异常.Ⅰ期患眼黄斑区结构正常,视网膜色素上皮(RPE)下小团块强反射病灶,可见浆液性视网膜脱离.Ⅱ、Ⅱa期患眼RPE-脉络膜毛细血管复合体(ORCC)呈弥漫性增厚隆起信号增强,黄色物质位于光感受器细胞内外节连接( IS/OS)与RPE层之间;Ⅱa期患眼RPE-ORCC增厚区域小,呈圆锥样隆起有弱反射区围绕.Ⅲ期患眼病灶上半部分表现为弱反射区,下半部分黄色物质表现为强反射并堆积于IS/OS与RPE层之间.Ⅳa期患眼病灶处神经感觉层下为无反射区,边界清晰,其下RPE-ORCC变薄,IS/OS光带及外界膜缺失.Ⅳb期患眼纤维化病灶RPE层增厚、隆起,呈强反射,视网膜神经上皮变薄和其上方广泛的IS/OS光带缺失.Ⅳc期患眼RPE连续性中断,可伴有黄斑部水肿.[结论]BVMD病灶中的黄色物质位于IS/OS与RPE层间,表现为强反射.Ⅱa期～Ⅳ期BVMD患眼的OCT典型图像特征为外核层与RPE层之间大小不一的腔隙样弱反射区伴或不伴有同一区间锥形强反射灶.     

脑源性神经营养因子对小鼠视网膜光损伤的防护

目的 探讨玻璃体腔注射脑源性神经营养因子(BDNF)对小鼠视网膜光损伤的防护作用及其机制.方法 120只小鼠随机分为正常对照(Ⅰ组)、光损伤对照组(Ⅱ组)、注射对照组(ⅢPBS组)和BDNF注射组(ⅢBDNF组).其中Ⅱ组、ⅢPBS组和ⅢBDNF组制成光损伤模型,通过光镜及电镜观察各组小鼠视网膜组织形态学改变,计算机图象分析视网膜外核层(ONL)厚度及凋亡指数(AⅠ).结果 Ⅰ组视网膜组织形态正常,结构层次分明,ONL厚度为(58.5139±1.2235)μm,AⅠ为0.其他各组均受到不同程度的损伤,但ⅢBDNF组各时间点损伤变化均较轻,感光细胞核排列紧密,内外节结构较清楚,仅部分线粒体肿胀,外节排列紊乱.光照后16、24、36、72 h ONL较Ⅱ组及ⅢPBS组厚,差异有统计学意义(P<0.01).ⅢBDNF 组在光照后16、24、36 h AⅠ均低于Ⅱ组及Ⅲ.组.凋亡高峰出现在光照后36 h,相对于Ⅱ组、ⅢPBS组峰值后延12 h,ⅢBDNF 组与Ⅱ组、ⅢPBS组两组比较,差异有统计学意义(P<0.01).另外,Ⅱ组及ⅢPBS组厚度随光照后时间的延长逐渐变薄,除24 h与36 h之间的比较(P>0.05)外,其余各时间点的比较,差异均有统计学意义(P<0.05).结论 光照可能引发内源性DNA修复机制,部分受损的DNA被修复.BDNF的玻璃体腔注射对小鼠视网膜光损伤有防护作用.     

曲安奈德对兔视网膜色素上皮细胞DNA 的损伤作用

目的观察曲安奈德(triamcinolone acetonide,TA)对兔视网膜色素上皮(retinal pigment epithelium,RPE)细胞DNA的损伤作用。方法应用单细胞凝胶电泳技术,分别测定0g.L-1、0.001g.L-1、0.01g.L-1、0.1g.L-1和1.0g.L-1TA作用于5组(空白对照组、Ⅰ组、Ⅱ组、Ⅲ组和Ⅳ组)兔RPE细胞24h后细胞DNA的损伤情况。结果兔RPE细胞在含有不同浓度TA的培养液中培养24h后,Ⅱ、Ⅲ和Ⅳ组的尾DNA含量、尾矩、Olive尾矩均高于空白对照组(10.40±2.83,9.72±3.45,12.73±3.38;12.24±4.34,10.45±5.99,12.72±5.07;17.37±5.00,17.62±5.95,20.02±5.72;P<0.05)。Ⅳ组的尾DNA含量、尾矩、Olive尾矩与Ⅰ组相比差异有统计学意义(P<0.05)。结论TA可导致兔RPE细胞DNA损伤且具有量效相关性。     

视网膜对形觉剥夺性近视鸡巩膜MMP-2的调控

目的建立鸡形觉剥夺性动物模型,通过观察用庆大霉素破坏小鸡视网膜后,后极部巩膜基质金属蛋白酶Ⅱ(matrix metalloproteinase-2,MMP-2)的变化,探讨视网膜在形觉剥夺性近视(formdeprivation myopia,FDM)发生、发展中的影响作用。方法48只白色来亨鸡(鸡龄2d,SPF级)分为A、B、C、D4组,每组12只,其中A组、B组在第2d即行双眼半透明眼罩遮盖同时行右眼玻璃体内1次注射庆大霉素400μg;C组仅右眼玻璃体内1次注射庆大霉素400μg不予遮盖,左眼不作处理为自身对照;D组不作任何处理,为正常对照组。在第3周末,对全部小鸡行检影验光测屈光度后,将A、C2组鸡处死,迅速摘除双眼球,测量其前后径。并随机取出2只送病理组织切片;B组摘除双眼眼罩后继续饲养3周,在第6周末对B、D2组行检影验光后将其处死,摘除双眼球测量眼球前后径。用7mm直径环钻钻取后极部巩膜组织,研磨离心后取上清液作为标本,对所有标本采用ELISA(即酶联免疫吸附)试剂盒测定MMP-2活性浓度。所有数据经过EXCEL和SPSS统计软件进行处理。结果第3周末,A、B两组双眼屈光度之间均具有显著性差异(P<0·001),C组和D组双眼屈光度间无显著性差异(P=0·088,0·920),且A、B2组与C组双眼屈光度比较均分别具有显著性差异(P<0·001);A组双眼眼轴测量值具有显著性差异(P<0.01),C组双眼眼轴未见显著性差异(P>0.05),A组与C组比较时,右眼眼轴无显著性差异(P>0.05),而左眼间差异具有显著性(P<0.001);第6周末,B组去遮盖后双眼屈光度及眼轴测量值之间均无显著性差异(P>0.05),且与D组比较差异亦无显著性意义(P>0.05),但B组去遮盖前后双眼屈光度之间具有明显显著性差异(P<0.001)。ELISA结果显示,除了A组双眼后级部巩膜MMP-2含量自身对照及与其他各组比较均有显著性差异外(P<0.001),另外3组之间差异均无显著性意义(P>0.05)。结论视网膜色素上皮层在形觉剥夺性近视的发生发展过程中起着非常重要的作用,破坏视网膜色素上皮层能一定程度的减轻近视的发展程度。     

急性中心性浆液性脉络膜视网膜病变三维光相干断层扫描图像特征

中心性浆液性脉络膜视网膜病变(CSC)是常见的眼底病变,荧光素眼底血管造影(FFA)可观察到CSC视网膜色素上皮(RPE)水平的"墨渍"状,"炊烟"状等不同状态的渗漏[1].二维光相干断层扫描(OCT)可显示CSC视网膜神经上皮层和RPE脱离反光带等视网膜横截面图像特征[2],但二维OCT只能反映单一视网膜切面,无法提供整个视网膜神经上皮层脱离区域的RPE脱离状况.     

急性中心性浆液性脉络膜视网膜病变三维光相干断层扫描图像特征

中心性浆液性脉络膜视网膜病变(CSC)是常见的眼底病变,荧光素眼底血管造影(FFA)可观察到CSC视网膜色素上皮(RPE)水平的"墨渍"状,"炊烟"状等不同状态的渗漏[1].二维光相干断层扫描(OCT)可显示CSC视网膜神经上皮层和RPE脱离反光带等视网膜横截面图像特征[2],但二维OCT只能反映单一视网膜切面,无法提供整个视网膜神经上皮层脱离区域的RPE脱离状况.     

猴光学离焦性与形觉剥夺性近视眼视网膜形态及超微结构比较

目的对比观察光学离焦性和形觉剥夺两种诱导方法所致恒河猴近视眼视网膜形态与超微结构的变化。方法年龄1.0～1.5个月的健康恒河猴15只,1只眼为实验眼配戴-3.00D镜片(9只眼)或散射镜片(6只眼),造成光学离焦或形觉剥夺;另1只眼作为对照眼。处理后不同时间用角膜地形图、睫状肌麻痹下验光、A超动态观察猴眼屈光状态和眼轴的变化;用相干光断层扫描术(OCT)动态观察视网膜厚度的变化,并与组织学测量值进行比较;3个月后,光镜和电镜下对比观察光学离焦、形觉剥夺性近视眼和对照眼视网膜超微结构的变化。结果15只猴实验眼均形成近视眼,光学离焦和形觉剥夺性近视眼视网膜均可见视杆细胞外节较长,视锥细胞膜盘减少,膜盘间隙增大,视网膜神经上皮层均较对照眼薄(均P<0.05);视网膜神经上皮层和色素上皮层厚度的OCT测量值与经校正后的组织学测量值比较差异均无统计学意义(P>0.05)。结论实验性近视眼视网膜超微结构与对照眼明显不同,但光学离焦和形觉剥夺性近视眼视网膜超微结构变化很相似。这种改变在近视眼发生、发展过程中的意义有待进一步探讨。     

Comparison of refractive state and circumferential morphology of retina, choroid, and sclera in chick models of experimentally induced ametropia.

PURPOSE: Simultaneous comparisons of the circumferential morphological tissue profiles and final refractions from form-deprivation myopia (FDM), defocus-induced myopia (DIM), and defocus-induced hyperopia (DIH) models of ametropia have been made to test the hypothesis that changes in the thickness profiles of the three coats of the eye, and particularly that of the choroid, can be predicted from the degree of induced refractive error. METHODS: Hatchling chickens (n = 23) were raised for 2 weeks wearing either a monocular translucent diffuser (FDM, n = 8), monocular -10.00 D lens goggle (DIM, n = 7), monocular +10.00 D lens goggle (DIH, n = 7), or nothing (Norm, n = 1). All animals were refracted using retinoscopy and were then sacrificed, and whole eyes were processed for scanning electron microscopy. Retinal, choroidal, and cartilaginous sclera (CS) thickness measurements were made from photographic collages of the entire circumference of the globe. Of the 23 chickens, complete morphological profile data were available for both eyes of 10 animals (nine treated and one normal). The contralateral fellow eyes (FEyes) of all nine experimental chickens were used as experimental controls as paired comparisons for statistical analyses. RESULTS: Morphological profiles of control and experimental eyes revealed significant systematic regional variations in tissue thickness. This variation was related to nasal or temporal eccentricity with the nasal side generally thinner than the temporal. Retinal, choroidal, and CS tissue from FDM and DIM eyes showed very similar anatomical responses despite significantly different degrees of refractive change. DIH eyes showed significant increases in choroidal thickness but none in retinal or CS thickness. Analysis of fellow control eyes indicated that in both myopia models (FDM and DIM), significant changes in all tissues of the untreated fellow eyes occur whereas only the choroid of the fellow eye was affected in the hyperopic (DIH) model. CONCLUSIONS: The morphological similarity observed in the circumferential profiles of the retina, choroid, and cartilaginous sclera of the FDM and DIM eyes despite approximately 20 D difference in final refraction suggests that choroidal thickness is not a good predictor of final refractive error across models. Similarly, the final refractive difference of approximately 20 D between the DIM and the DIH eyes did not receive a major contribution from the final difference in choroidal thickness (with its implied effect on vitreous chamber length).     

Experimental eye enlargement in mature animals changes the retinal pigment epithelium.

Form deprivation has been shown to result in myopia in a number of species such that the eye enlarges if one eye is permanently closed at the time of eye opening. In the quokka wallaby, the eye grows slowly throughout life. After form deprivation, the eye enlarges by 1-1.5 years of age to the size of that in a 4-6-year-old animal and the number of multinucleated retinal pigment epithelial (RPE) cells in the enlarged retina remains much lower than would be expected in eyes of comparable size. Here we have repeated the experiment but examined animals at 4 years of age. The sutured eye grew significantly larger than did its partner. Numbers of RPE cells were comparable between sutured and partner eyes but were lower than in normal animals of similar age. Reductions in RPE cell density were greater in nasal than in dorsal or ventral retina and were not seen in temporal retina. The distribution of multinucleated cells was quite different in the sutured and open eyes. As in normal eyes, partner eyes had most multinucleated cells in ventral retina, while in the sutured eyes such cells were located mainly in the far periphery. In conclusion, the RPE is significantly changed by the eye enlargement process. However, it is not known whether this change results from an active part played by the RPE in the retinal expansion process or whether the changes are simply a result of a passive increase in area of the RPE.     

Retinoic acid metabolic change in retina and choroid of the guinea pig with lens-induced myopia

AIM: To investigate the role of retinoic acid (RA) and retinaldehyde dehydrogenase-2 (RALDH₂) of retina and choroid in the guinea pig lens-induced myopic eyes. METHODS: Totally 45 guinea pigs, at age of three weeks, were randomly assigned into three groups: the normal control, the lens-induced group and the recovering group. Out of focus was induced by the -6.00D concave lens on the left eye, and lasted for 15 days. All animals underwent biometric measurement (corneal radius of curvature, refraction and axial length). Subsequently, RA content in the retina and RPE/choriod complex was detected by reversed-phase high-performance liquid chromatography. RALDH₂ protein in the retina and RPE/choriod complex was evaluated by the immunohistochemical staining and Western blotting. RESULTS: After wearing -6.00D lens for 15 days, axial length of the lens-induced eye extends and myopia was formed, with RA contents increasing in both the neural retina and RPE/choroid complex. Comparing with the lens-induced group, myopic degree significantly relieved, and its RA contents in both the neural retina and RPE/choroid complex decreased in the recovering group. In the normal control, RALDH2 protein was expressed positively in the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL) and lateral border of outer nuclear layer (ONL). Retinal RALDH₂ protein increased in the lens-induced group, and was also positive in the outer plexiform layer (OPL). In the recovering group, retinal RALDH₂ protein attenuated the expression in the OPL turns to negative. RALDH₂ protein was not expressed in the choroid of any group. CONCLUSION: RA of retina and chorid participates in the regulation of the lens-induced myopia in guinea pigs, which may be related with retinal RALDH2 protein.     

Structural and elemental evidence for edema in the retina, retinal pigment epithelium, and choroid during recovery from experimentally induced myopia

PURPOSE: The purpose of this study was to monitor temporal changes in the retina, retinal pigment epithelium (RPE), and choroid of chick eyes using biometric, ultrastructural, and elemental microanalysis techniques as a means of visualizing more detailed signs of the physiological processes underlying choroidal expansion and refractive normalization during recovery from form deprivation. METHODS: Axial dimensions and refractions were measured on form-deprived and fellow eyes of 117 experimental chickens reared with monocular translucent occlusion from days 1 to 15 and given different lengths of visual experience (T = 0-144 hours) before death. Tissue was analyzed ultrastructurally by electron microscopy and relative sodium (Na) and chloride (Cl) ion abundances, by using x-ray microanalysis to determine changes in the presence of these indicators of tissue hydration. RESULTS: Refractive error decreased from more than 20 D of myopia almost linearly over the first 144 hours after occlusion. Concurrent changes in thickness in the retina, RPE, and choroid were seen as a series of thickness increases and edema, which returned to normal thickness, first in the retina, and did not reach maximum until 3 days after occluder removal in the choroid. In freeze-dried tissue, Na and Cl ion concentrations were greatest in the RPE photoreceptor outer segments and extravascular choroid at T = 0, decreasing toward fellow eye levels by T = 48 in the RPE and choroid. Na and Cl ion abundances in the frozen lymph of choroidal lymphatics were nearly at control levels (T = 0) and increased later as the vessels became more distended after the extravascular edema became significant. CONCLUSIONS: The results suggest that occluder removal induces edema across the retina and choroid and that this fluid may be the vector eliciting choroidal expansion during recovery from form deprivation possibly driven by the hyperosmolarity in the choroid, RPE, and photoreceptor outer segments that accompanies deprivation.     

Effects of nicotinic antagonists on ocular growth and experimental myopia

PURPOSE. To learn whether nicotinic cholinergic receptors modulate postnatal eye growth and influence the course of form-deprivation myopia. METHODS. One-week-old White Leghorn chicks wore a unilateral goggle to induce form-deprivation myopia. Other chicks were never goggled. Nicotinic antagonist drugs were administered by intravitreal injection, usually daily or every other day to the goggled eye or to one eye of never-goggled chicks. After 1 week, the eyes were studied by refractometry, A-scan ultrasonography, and caliper measurements. RESULTS. The relatively non-subtype-specific channel-blocking nicotinic antagonists chlorisondamine and mecamylamine each inhibited the development of form-deprivation myopia but with complex multiphasic dose responses. Chlorisondamine was the most effective. Mecamylamine, at the lowest tested doses, tended to stimulate the growth response and myopic refractive shift of goggle wearing. Methyllycaconitine competitively inhibits nicotinic receptors containing the alpha7 and alpha8 subunits, which are highly expressed in chick retina. It showed a less dramatic but still significant inhibitory effect on myopia. The effects of dihydro-beta-erythroidine, a competitive antagonist relatively selective for nicotinic receptors with alpha3 or alpha4 subunits and particularly for alpha3beta2-containing receptors, were the weakest and inhibited primarily axial elongation. Chlorisondamine but not mecamylamine also affected nongoggled eyes, inhibiting growth and shifting refraction toward hyperopia, but chlorisondamine also induced degenerative changes to the retinal pigment epithelium (RPE). CONCLUSIONS. Nicotinic receptors are involved in eye growth control. Nicotinic antagonists affect the development of form-deprivation myopia and perhaps the growth of nongoggled eyes. The differences in drug activity and multiphasic dose-response curves may reflect the complexity of nicotinic receptor subtypes associated with the eye and/or pharmacokinetic differences between the individual drugs. Although another tissue(s) cannot be completely excluded by these data, the site of action of these agents may be neural retina or RPE.     

Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets

PURPOSE: The purpose of this study was to examine the possibility that all-trans-retinoic acid (RA) in the eye is a signal related to changes in scleral extracellular matrix in a primate model of postnatal eye growth. METHODS: Juvenile marmosets (Callithrix jacchus) were divided into two experimental groups based on their response to monocular deprivation with diffusers: group 1, treated eyes becoming longer than fellow control eyes (n = 8), and group 2, treated eyes becoming shorter than control eyes (n = 7). Eyes were enucleated, dissected, and assayed for changes in the rates of scleral glycosaminoglycan (GAG) synthesis and ocular RA synthesis. The rate of incorporation of (35)SO4 into CPC-precipitable GAG in scleras was taken as a measure of the rate of synthesis of proteoglycans. In the same eyes the rate of RA synthesis in vivo was measured separately in the retina and the choroid/RPE (choroid with RPE attached) by HPLC. The effect of RA on the rate of scleral GAG synthesis was also examined in tissue-cultured pieces of sclera from additional marmosets. RESULTS: Induced changes in vitreous chamber length in diffuser-treated eyes correlated inversely with the rate of scleral GAG synthesis (P < 0.05) and directly correlated with the rate of RA synthesis measured separately in the retina (P < 0.05) and the choroid/RPE (P < 0.05). In group 1, the rate of scleral GAG synthesis was significantly lower (P < 0.01) in the treated eyes relative to control eyes, and the rate of RA synthesis in both the retina and the choroid/RPE was significantly higher (P < 0.01). In group 2, the rates of scleral GAG synthesis and RA synthesis in either the retina or choroid/RPE were not found to change significantly in the treated eyes compared with the control eyes. RA partially reduces the rate of scleral GAG synthesis in tissue-cultured primate sclera in a dose-dependent manner after several days. CONCLUSIONS: RA may play a role in the visual control of postnatal eye growth in primates, possibly by inducing changes in scleral extracellular matrix associated with increasing eye size. Decreasing growth rate below control levels may involve other mechanisms.     

Bidirectional, Optical Sign-Dependent Regulation of BMP2 Gene Expression in Chick Retinal Pigment Epithelium

Purpose. We explored the role of bone morphogenic protein 2 (BMP2) in defocus-induced ocular growth using gene expression changes in RPE as a surrogate. Methods. Young White-Leghorn chickens were used in this study. Normal gene expression of BMP2 and its receptors was examined in retina, RPE, and choroid, and BMP2 protein expression assessed in the same tissues using Western blots and immunohistochemistry. Quantitative PCR (qPCR) was used to assess the effects of short-term exposure (2 or 48 hours) to monocular +10 and -10 diopter (D) lenses, on RPE gene expression of BMP2 and its receptors. Ocular growth was assessed using A-scan ultrasonography. Results. In the eyes of untreated chickens, BMP2 mRNA was expressed more highly in RPE compared to retina and choroid and all three tissues expressed BMP2 protein. The gene expression for all three receptors also was detected in these tissues, with BMPR2 showing highest and BMPR1B lowest expression. BMP2 was up-regulated in the RPE from eyes wearing +10 D lenses, which exhibited shorter than normal vitreous chambers (VCDs) and thickened choroids, while BMP2 was down-regulated in the RPE from eyes wearing -10 D lenses, which developed enlarged VCDs. These treatments did not induce differential expression of BMP receptors in RPE. Conclusions. That mRNA expression of BMP2 in chick RPE shows bidirectional, defocus sign-dependent changes is suggestive of a role for BMP2 in eye growth regulation, although the diffuse ocular expression of BMP2 and its receptors suggests complex growth-modulatory signal pathways.     

Pediatric rhegmatogenous retinal detachment in taiwan

PURPOSE: To describe the clinical features and surgical outcomes in a series of pediatric patients with rhegmatogenous retinal detachments in Taiwan. METHODS: Retrospective study of pediatric patients (age 1 to 15 years) with rhegmatogenous retinal detachment dated between January 1995 and December 2004. Patients with perforating ocular trauma were excluded. Patients were divided into four groups according to the predisposing factors: Group 1, those with congenital or developmental anomalies; Group 2, those with trauma history; Group 3, those with myopia greater than -3 D but excluding patients in Groups 1 and 2; and Group 4, the others with miscellaneous etiologies. Patients' age, sex, medical history, ocular history, type of detachment, macular status, refractive status, previous visual acuity, number and type of surgeries performed, postoperative retinal status, and current visual acuity were recorded. RESULTS: Thirty-five eyes of 32 patients were included in this study. The median age was 13 years, and 75% of patients were boys. There were 17 eyes (49%) in Group 1, 8 in Group 2 (23%), 8 in Group 3 (23%), and 2 in Group 4 (6%). Bilateral retinal detachment was present in 7 patients (22%). In Group 1, familial exudative vitreoretinopathy was present in 7 eyes; retinopathy of prematurity was noted in 5 eyes; Marfan's syndrome was present in 3 eyes; mental and growth retardation was present in 2 eyes. Macula sparing retinal detachment was found in 3 eyes. Retinal attachment was achieved in 28/35 eyes. Visual recovery was modest. CONCLUSION: Congenital or developmental anomalies, myopia, and trauma were the most common risk factors for pediatric rhegmatogenous retinal detachment in Taiwan. Regular follow-up for children at risk of developing rhegmatogenous retinal detachment is necessary for early detection.