锂对视网膜色素变性小鼠光感受器细胞凋亡的保护作用

目的 研究锂在视网膜色素变性小鼠模型上对光感受器细胞凋亡的神经保护作用.方法 实验研究.FVB/NJ视网膜色素变性小鼠出生后立刻用含锂的食物喂养,7和14 d时摘除眼球做视网膜冰冻切片,同时取血测血清锂浓度.HE、TUNEL和视杆细胞免疫荧光染色进行视网膜组织形态、光感受器细胞凋亡分析.结果 光镜下可见,对照组外核层可见TUNEL阳性细胞,出生后14 d外核层厚度和细胞层数(3或4层)明显低于7 d时的厚度(9或10层),而锂喂养组出生后14 d外核层的厚度和细胞层数明显高于对照组,与出生7 d时的外核层厚度及细胞层数无明显差异.结论 锂能够保护视网膜色素变性小鼠光感受器细胞免于凋亡.(中华眼科杂志,2008,44:248-252)     

视网膜色素变性光感受器的组织病理学观察

目的：研究视网膜色素变性光感受器的组织病理学改变。 方法：对9例11眼视网膜色素变性的光感受器进行光学和电子显微镜观察。 结果：发现赤道部光感受器病理损害最明显，其次为周边区、后极部和黄斑。中期病例病理改变包括外节盘膜退变、变小和连接纤毛减少或消失；内节粗短、线粒体肿胀。晚期病例内、外节和纤毛消失，外界膜粘附在色素上皮细胞或Bruch膜上。光感受器细胞核减少、排列紊乱，细胞变性、结构破坏。移位的Müller细胞和增生肥大的细胞突占据了内外节和光感受器细胞核消失所遗留的空间。色素上皮细胞退变，部分消失或移位到视网膜内。结论：视网膜色素变性光感受器有明显损害。 （中华眼底病杂志，1996，12：160-162）     

视网膜色素变性的研究进展

视网膜色素变性(retinitis pigmentosa,RP)是常见的与遗传相关的致盲性眼病之一,随着人类基因图谱的成功建立,它成为近几年国内外基础医学和临床医学共同的研究热点。本文回顾十余年来国内外特别是国外相关文献,对视网膜色素变性的发病机制、治疗方法的研究进展作一综述。     

视网膜色素变性治疗进展

视网膜色素变性(RP)是一组以光感受器细胞进行性变性为特征,具有高度遗传异质性的致盲眼病,目前尚无有效方法阻止或逆转其进程.近年来随着对RP分子发病机制认识不断深入,RP基因治疗取得了初步成功;针对不同发病环节的抗凋亡、神经保护等多种治疗手段被尝试;而以干细胞为基础的移植治疗和视觉假体植入则为晚期患者带来了希望.     

视网膜色素变性基因治疗的研究现状及展望

视网膜色素变性(RP)发生与基因变异有着密切关系.探寻RP致病基因及分子发病机制;通过RP基因治疗延缓或阻止感光细胞的损失,保护视功能已成为研究热点.对某些基因突变类型进行RP基因治疗临床试验是今后值得重视的课题.     

中国视网膜色素变性相关基因研究现状

目的 分析20年来中国视网膜色素变性(RP)相关基因研究现状。方法 回顾性分析。通过检索中国知网(CNKI)中国学术文献网络出版总库、美国国家生物技术信息中心、人类基因突变数据库、人类基因组变异协会等数据库及查阅1991～2011年发表的相关文献,统计已研究的RP相关基因种类和研究结果,并与国外相关研究进行对比。结果 迄今已发现60个与RP相关的基因。我国自1991年开始开展RP相关基因的筛查。迄今为止,共有29所医院和研究机构,收集300个RP家系和1572例散发型RP患者,对17个RP相关基因进行了研究,发表RP基因突变的文献66篇,发现239个突变,其中致病性突变131个;关于基因治疗的文献有4篇。我国RP患者中,视紫红质(RHO)、特异性光感受器细胞核受体和RP1基因突变的发生率分别为2.0％、2.9％和1.0％。关于RP基因型与临床表型关系的研究较少,发表文献15篇,主要集中在ADRP致病基因RHO、视网膜变性慢(RDS)、RP1和RP三磷酸鸟苷酶调节子(RPGR,又名RP3)的突变热点区域。国外关于RP基因筛查的文献有718篇,发现2000多个突变,其中致病性突变352个;关于RP基因治疗的文献有391篇。RHO、RDS和RP1基因是导致白种人群ADRP最主要的3个基因,基因突变的发生率分别为25％～50％、8％、5％～10％。RPGR基因是导致白种人群XLRP最主要的基因,基因突变的发生率为70％～80％,其中外显子开放阅读框15的突变频率最高,约为50％～60％。结论 我国已对17个RP相关基因进行了研究,发现了131个致病性突变;RP基因治疗尚处于起步阶段。与国外研究相比存在较大差距。     

米诺环素对视网膜色素变性小鼠光感受器细胞的保护作用

目的 观察米诺环素对视网膜色素变性（RP）的rd小鼠［C3H/HeN (Pde6brd-/rd-)］RP过程的影响。方法 40只新生rd小鼠随机分为10组，5组为实验组，5组为对照组，每组4只小鼠。实验组，出生后每日腹腔注射米诺环素22.5 mg/kg；对照组，出生后每日腹腔注射生理盐水10 ml/kg。在出生后1、7、14、21、28 d各处死一组实验组和对照组小鼠，取眼球做组织学观察并行凋亡细胞检测，并对两组视网膜光感受器细胞数、外核层厚度以及凋亡细胞数目进行统计分析。结果 （1）rd小鼠出生后7 d光感受器细胞开始凋亡，14 d达高峰，28 d光感受器细胞完全消失；（2）出生后7 d实验组光感受器细胞数目和外核层厚度与对照组比较差异无统计学意义；（3）出生后14、21 d实验组光感受器细胞数目和外核层厚度多于对照组相应时间点，差异有统计学意义（14 d：t=-3.03、P=0.016，t=-4.469，P=0.004；21d: t=-8.782、P＜0.001，t=-3.497、P=0.004）；（4）出生后7、14 d实验组外核层凋亡细胞数目少于对照组相应时间点，差异有统计学意义（t=-3.497、P=0.004，t=-8.782、P＜0.0001）。结论 米诺环素在rd小鼠RP早期可以延缓光感受器细胞丢失，但不能完全阻止RP的发生。     

细胞周期蛋白依赖激酶5与皇家外科学院大鼠视网膜色素变性发病过程中细胞凋亡的关系

目的 观察细胞周期蛋白依赖激酶5(Cdk5)和p25在不同病程皇家外科学院(RCS)大鼠视网膜色素变性(RP)模型视网膜中的表达及与细胞凋亡的关系,探讨Cdk5/p25介导的光感受器细胞凋亡在RP发病过程中的作用.方法 取RCS RP大鼠(RCS大鼠)及正常对照RCS-rdy+大鼠17、25、35、60日龄视网膜,光学显微镜下观察视网膜结构,测量外核层厚度;利用免疫组织化学染色法观察视网膜中Cdk5、p25和活化型半胱氨酸天冬氨酸蛋白酶3(cleave-caspase 3)的表达和变化;采用Western blot法测定视网膜中cleave-caspase 3的蛋白质水平;原位末端标记(TUNEL)法检测视网膜中凋亡发生的情况,并对凋亡细胞平均吸光度[A,旧称光密度(OD)]值进行统计分析.采用SPSS 17.0统计软件处理数据.结果 随着出生日龄的增加,RCS大鼠视网膜厚度较RCS-rdy+大鼠变薄,主要表现为视杆与视锥层和外核层明显变薄.在RCS大鼠17、25、35日龄组,Cdk5、p25和cleave-caspase 3的表达逐渐增强,60日龄组表达下降;对照组RCS-rdy+大鼠各日龄组表达无明显变化.Western blot法检测结果显示,随着出生日龄的增加,RCS大鼠各日龄组视网膜cleave-caspase 3的表达明显增加,以35日龄组增加最为明显,而RCS-rdy+大鼠各日龄组视网膜cleave-caspase 3的表达没有明显的变化.TUNEL法检测结果显示,凋亡细胞主要出现在外核层中,在RCS大鼠17、25、35日龄组,各组凋亡细胞呈逐渐增多的趋势,60日龄组凋亡细胞显著下降;RCS-rdy+各日龄组凋亡细胞没有明显变化.多变量偏相关分析结果显示,Cdk5表达与p25表达、Cdk5表达与cleave-caspase 3表达、Cdk5表达与凋亡细胞表达、p25表达与cleave-caspase 3表达、p25表达与凋亡细胞表达、cleave-caspase 3表达与凋亡细胞表达的偏相关系数分别为0.949、0.808、0.959、0.887、0.979、0.852,P值为0.000,两两变量之间均显著相关.结论 17、25、35日龄RCS大鼠,随着出生日龄的增加,其视网膜凋亡细胞逐渐增多,而Cdk5、p25和cleave-caspase 3的表达逐渐增强.RCS大鼠视网膜中凋亡细胞变化趋势与Cdk5、p25和cleave-caspase 3的表达基本一致.提示RCS大鼠视网膜中光感受器细胞的凋亡与Cdk5、p25的表达水平升高有关,Cdk5可能参与RCS大鼠RP的发生与发展.     

川芎嗪对氧诱导视网膜病变中视网膜神经细胞凋亡的抑制作用

目的 观察川芎嗪(TMP)对氧诱导视网膜病变(OIR)中视网膜神经细胞凋亡的抑制作用.方法 48只C57BL/6新生幼鼠随机分为正常对照组、OIR对照组及OIR药物组,分别为18、18、12只.正常对照组在正常空气环境中饲养.OIR对照组、OIR药物组幼鼠于出生后7 d置于含氧体积分数(75±3)%的氧气箱中连续生活5 d;出生后12 d,幼鼠回到正常空气环境中饲养,建立OIR模型.出生后12～16d,OIR药物组按200 mg/kg的剂量腹腔注射TMP,1次/d;正常对照组、OIR对照组同时注射相同体积的含0.1%二甲基亚砜(DMSO)的生理盐水.出生后12、14、17 d,摘除幼鼠眼球作石蜡切片并行苏木精-伊红(HE)和脱氧核苷酸末端转移酶介导缺口末端标记(TUNEL)染色.观察视网膜无灌注区形态学变化,检测视网膜神经细胞凋亡数量.结果 正常对照组幼鼠视网膜各层结构清晰.出生后12 d,OIR对照组幼鼠视网膜内核层(INL)可见少量染色质凝聚的细胞核.出生后14 d,OIR对照组幼鼠视网膜INL可见大量染色质凝聚的细胞核,OIR药物组幼鼠视网膜INL均可见少量染色质凝聚的细胞核.出生后17 d,OIR对照组幼鼠视网膜INL、内丛状层(IPL)和外丛状层(OPL)厚度变薄;OIR药物组幼鼠视网膜中周部INL、IPL和OPL厚度较正常对照组薄,较OIR对照组厚.出生后12 d,OIR对照组幼鼠视网膜TUNEL阳性细胞数量为正常对照组的6倍,差异有统计学意义(t=9.432,P＜0.001).出生后14 d,3组幼鼠视网膜TUNEL阳性细胞数量比较,差异有统计学意义(F=587.217,P＜0.001);OIR对照组幼鼠视网膜TUNEL阳性细胞数量为正常对照组的28倍,差异有统计学意义(t=49.813,P＜0.001);OIR药物组幼鼠视网膜TUNEL阳性细胞数量较OIR对照组减少了82.3%,差异有统计学意义(t=42.434,P＜0.001).出生后17 d,3组幼鼠视网膜TUNEL阳性细胞数量比较,差异无统计学意义(F=587.217,P>0.05).结论 TMP能明显抑制OIR中视网膜神经细胞凋亡.

Abstract：

Objective To observe the inhibitory effect of tetramethylpyrazine(TMP)on apoptosis of retinal neurons in oxygen-induced retinopathy(OIR).Methods 48 C57BL/6 mice were randomly divided into normal control group(n=18),OIR control group(n=18)and OIR TMP group(n=12).The mice of normal control group were raised in room air.From the postnatal day 7(P7),mice of the other two groups mice of OIR TMP group received intraperitoneal injection of TMP(200 mg/kg)once a day from P12 to P16.meanwhile the mice of normal control group and OIR control group were iniected with the same volume of normal saline containing of 0.1% DMSO.At P12,P14 and P17,the morphologic changes in retinal avascular zone and the number of retinal apoptotic cell were observed by HE staining and TUNEL assay.Results At P1 2.there were a few of chromatin condensation and pycnic nuclei in the inner nuclear layer (INL)of OIR control group.At P14,a great quantity(OIR control group)or some(OID TMP treated group)chromatin condensation and pycnic nuclei in the central INL were observed.At P17,the thickness of INL,inner plexiform layer(IPL)and outer plexiform layer(OPL)in the OIR control group were reduced;the thickness of INL,IPL and OPL in the OIR TMP group weas thinner than those in the normal control group and thicker than those in the OIR control group.At P12,the TUNEL-positive cells in the OIR control group was 6 times of the normal eontrol group(F=587.217,P＜0.001).At P14,the difference of TUNEL-positive cells in three groups was significant(F=587.217,P＜0.001);the TUNEL-positive cells in the OIR control group was 28 times of the normal control group(t=49.813,P＜0.001);the TUNEL-positive cells in the OIR TMP group has reduced 50% compared with the OIR controI group(t=42.434,P＜0.00 1).At P17,there was no significant difference in TUNEL-positive cells among the three groups (F=587.217,P>0.05).Conclusions TMP can inhibit apoptosis of retinal cells in OIR significantly.     

川芎嗪对氧诱导视网膜病变中视网膜神经细胞凋亡的抑制作用

Objective To observe the inhibitory effect of tetramethylpyrazine(TMP)on apoptosis of retinal neurons in oxygen-induced retinopathy(OIR).Methods 48 C57BL/6 mice were randomly divided into normal control group(n=18),OIR control group(n=18)and OIR TMP group(n=12).The mice of normal control group were raised in room air.From the postnatal day 7(P7),mice of the other two groups mice of OIR TMP group received intraperitoneal injection of TMP(200 mg/kg)once a day from P12 to P16.meanwhile the mice of normal control group and OIR control group were iniected with the same volume of normal saline containing of 0.1% DMSO.At P12,P14 and P17,the morphologic changes in retinal avascular zone and the number of retinal apoptotic cell were observed by HE staining and TUNEL assay.Results At P1 2.there were a few of chromatin condensation and pycnic nuclei in the inner nuclear layer (INL)of OIR control group.At P14,a great quantity(OIR control group)or some(OID TMP treated group)chromatin condensation and pycnic nuclei in the central INL were observed.At P17,the thickness of INL,inner plexiform layer(IPL)and outer plexiform layer(OPL)in the OIR control group were reduced;the thickness of INL,IPL and OPL in the OIR TMP group weas thinner than those in the normal control group and thicker than those in the OIR control group.At P12,the TUNEL-positive cells in the OIR control group was 6 times of the normal eontrol group(F=587.217,P＜0.001).At P14,the difference of TUNEL-positive cells in three groups was significant(F=587.217,P＜0.001);the TUNEL-positive cells in the OIR control group was 28 times of the normal control group(t=49.813,P＜0.001);the TUNEL-positive cells in the OIR TMP group has reduced 50% compared with the OIR controI group(t=42.434,P＜0.00 1).At P17,there was no significant difference in TUNEL-positive cells among the three groups (F=587.217,P>0.05).Conclusions TMP can inhibit apoptosis of retinal cells in OIR significantly.     

Long-term effect of acetazolamide in a patient with retinitis pigmentosa

The authors studied the therapeutic effect of acetazolamide on a patient with autosomal dominant retinitis pigmentosa complicated by retinal edema. In addition to reduction of macular edema and some improvement of central vision, they found an unexpected progressive increase in extrafoveal retinal sensitivity with prolonged medication. It is proposed that the therapeutic effect is mediated by alteration of retinal pigment epithelial function and that disturbed polarity is restored to a more normal state.     

Mobility performance with retinitis pigmentosa

Purpose : Reduced mobility can have a serious impact on quality of life. Though previous studies have demonstrated that some vision measures relate to the mobility of subjects with simulated and true low vision, the relationship between residual vision and mobility is not clear. We investigated the relationship between clinical vision measures and mobility performance under different illumination levels for subjects with retinitis pigmentosa (RP). Methods : Binocular visual acuities, letter contrast sensitivities and static central threshold visual fields were measured on 10 subjects with RP and nine age-matched control subjects. Mobility performance was measured on an indoor mobility course at high and low illuminances and was assessed by percentage preferred walking speed (PPWS) and number of errors. Results : The RP group showed significantly reduced PPWS and greater numbers of errors than the control group. The reduction in illumination resulted in significantly worse error and PPWS scores. Unlike the control group, the presence of a glare source did not reduce the PPWS of the RP group under high illumination. Multiple regression analyses showed that the average visual field extent was the most significant predictor of mobility; letter contrast sensitivity and visual acuity added to the regression models for the low illumination measures to account for up to 75 per cent of the variation in mobility performance. Conclusions : People with RP have worse mobility than people with normal vision, more so under reduced illumination levels. Visual field extent was the strongest predictor of mobility performance. (Clin Exp Optom 1996; 80: 1: 1–12)     

视网膜色素变性患者复明的希望

视网膜色素变性（RP）是一种遗传性视网膜疾病,其典型的临床表现为早期视杆细胞的退行性病变以及视锥细胞胞体相对长期的存活。目前实验研究证实,通过腺相关病毒载体和慢病毒载体将微生物型的光敏感通道蛋白channelrhodopsin-2或halorhodopsins导入RP模型鼠的视锥细胞胞体或其他细胞,可以使这些细胞获得光反应并激活视网膜传导通路,向视觉中枢传递视觉信息。因此,这为RP患者的复明带来了希望。     

Weill-Marchesani syndrome associated with retinitis pigmentosa

Retinitis pigmentosa (RP) is associated with a wide variety of ocular and systemic disorders. The Weill-Marchesani syndrome is a multi-system disorder with microspherophakia as one of the common manifestations. A 14-year-old girl presented with short stature, short and stubby fingers, hypodontia and low-set ears. Slit-lamp examination revealed microspherophakia, with shallow anterior chambers with irido and phacodonesis. Ultrasonographic biomicroscopy confirmed the clinical findings and revealed hypoplastic ciliary body. Electroretinogram confirmed the diagnosis of RP. Though RP has been associated with ectopia lentis in earlier reports, this is, to the best of our knowledge, the first case report describing the association of RP and Weill-Marchesani syndrome.     

Asymmetric retinitis pigmentosa, luetic retinopathy and the question of unilateral retinitis pigmentosa.

A seropositive patient with the fundus appearance of monocular luetic retinopathy is presented. Electrophysiologically, this patient shows a late-onset form of progressive tapetoretinal degeneration (retinitis pigmentosa) presenting in an extremely asymmetric manner. The differential diagnosis of luetic and other inflammatory retinopathies vs. tapetoretinal degenerations is briefly discussed. Features distinguishing unilateral retinitis pigmentosa from bilateral tapetoretinal degenerations are reviewed, and the existence of unilateral retinitis pigmentosa as a genetic entity is questioned. Prolongation of ERG- a- and b-wave implicit times is characteristic of the tapetoretinal degenerations, and normal implicit times in the fellow eye are suggested as an additional criterion for the diagnosis of unilateral retinitis pigmentosa.     

Cyclic exotropia associated with retinitis pigmentosa

Purpose To report the occurrence of cyclic exotropia in a patient with retinitis pigmentosa. Methods A 31-year-old man presented with cyclic exotropia of the left eye of 4 years duration that alternated every 24 h. A detailed ophthalmologic examination was performed. Results The patient showed an orthotropia and a comitant left exotropia of 30 prism diopters at distance and 25 prism diopters at near in the primary position on an exotropic day with a cycle of 48 h. A fundoscopic examination showed bone spicule formation and arteriolar narrowing, and electroretinography showed no response in either eye. A Goldmann visual field examination showed a central island in both eyes. Conclusions Cyclic exotropia may occur in patients with retinitis pigmentosa, an association that to the best of our knowledge has not been previously reported in the English ophthalmic literature. Cyclic exotropia is an unusual association with retinitis pigmentosa.