常染色体显性遗传视网膜色素变性患者视紫红质基因突变的研究

目的探讨常染色体显性遗传型视网膜色素变性(autosomal dominant retinitis pigmentosa,ADRP)患者视紫红质(rhodopsin,RHO)基因是否存在突变。方法应用聚合酶链反应(polymerase chain reaction,PCR)扩增RHO第1、5外显子基因片段，以限制性核酸内切酶酶切消化技术检测38个ADRP家系的57名患者和60名正常对照者RHO第58、347密码子的突变。结果1个ADRP家系的4名患者第58密码子发生点突变，另2个ADRP家系的6名患者第347密码子也出现点突变，而对照者未发现上述两种突变。结论ADRP存在分子水平的遗传异质性，某些ADRP是由于RHO基因突变所致。(中华眼底病杂志,1998,14:108-110)     

视网膜色素变性中医治疗及研究进展

视网膜色素变性(retinitis pigmentosa,RP)是一类以进行性感光细胞和色素上皮细胞功能障碍为特征的遗传性疾病,是世界范围内常见的致盲性眼病且至今缺乏有效的治疗方法。作者总结了近5年来中医治疗视网膜色素变性临床及实验研究进展,并提出了中医治疗视网膜色素变性的展望和面临的挑战。     

Reported effects of non‐traditional treatments and complementary and alternative medicine by retinitis pigmentosa patients

Background: Benefits of complementary and alternative medicine (CAM)‐related interventions have been demonstrated for patients with chronic, systemic diseases in which stress, anxiety and disability are prevalent. Subjects with retinitis pigmentosa (RP) commonly indicate that they have ‘good’ and ‘bad’ vision days, stating that stress causes a decrease in vision and that vision improves when the stress is alleviated. We assessed CAM use by RP patients and its perceived effectiveness. Methods: We enquired about nine CAM areas: meditation, mind‐body therapies, yoga, movement therapies, energy therapies, acupuncture, massage therapy, spirituality/religion and herbal therapies/aromatherapy. Ninety‐six RP patients with any level of vision completed an anonymous internet survey. Results: Ninety‐five per cent of respondents tried at least one of the nine CAM areas. Seventy‐five per cent have used nutritional supplements, including lutein (47 per cent), bilberry (32), vitamin A palmitate (36) and docosahexaenoic acid (23 per cent). Some tried meditation (47) and yoga (31 per cent). Stress and anxiety levels were reported as improved in 93, 92 and 87 per cent of those who used yoga, meditation and mind‐body therapies, respectively. Many of those who tried mind‐body therapies (40) or acupuncture (50 per cent), used it with a desire to fight RP. Vision was subjectively affected in 65 per cent of acupuncture users and from 20 to 35 per cent of the users of the other CAM areas. Those who indicated that their vision was affected by at least one type of CAM (35 per cent) were statistically significantly more likely to require magnification to read (that is, they had lost more vision and RP had progressed), than those who did not believe vision was impacted (59 versus 84 per cent). Conclusions: RP patients are using CAM and are experiencing some impact on vision and physical/emotional well‐being. Clinicians and researchers should be aware of its use. Clinical trials with CAM interventions are necessary to attempt to validate these findings.     

Xenopus laevis P23H rhodopsin transgene causes rod photoreceptor degeneration that is more severe in the ventral retina and is modulated by light

Rhodopsin transgenes carrying mutations that cause autosomal dominant retinitis pigmentosa in humans have been used to study rod photoreceptor degeneration in various model organisms including Xenopus laevis. To date, the only transgenes shown to cause rod photoreceptor degeneration in Xenopus laevis have been either mammalian rhodopsins or chimeric versions of rhodopsin based mainly on Xenopus laevis rhodopsin sequences but with a mammalian C-terminus. Since the C-terminal sequence of rhodopsin is highly conserved in mammals and divergent in Xenopus laevis, and mammalian and epitope-tagged rhodopsins may have unexpected properties as transgenes, we decided to test whether a Xenopus laevis rhodopsin transgene carrying only the P23H mutation could also cause rod photoreceptor degeneration. Xenopus laevis tadpoles expressing these transgenes indeed had shortened outer segments and, in severely affected animals, the loss of rod photoreceptors but not the loss of cone photoreceptors. RT-PCR analyses showed that less than 10% of mutant transgenic rhodopsin relative to wild-type endogenous rhodopsin mRNA was sufficient to produce severe rod photoreceptor degeneration. As observed in other animal models as well as humans carrying this particular rhodopsin mutation, the rod photoreceptor degeneration was most severe in the ventral retina and was modified by light. Thus, the rod photoreceptor degeneration produced in Xenopus laevis by the P23H mutation in an otherwise untagged Xenopus laevis rhodopsin is generally similar to that seen with mammalian rhodopsins and epitope-tagged versions of Xenopus laevis rhodopsin, though some differences remain to be explained.     

A case of Creutzfeldt-Jakob disease related to familial retinitis pigmentosa patients

Similarities between serological alterations and retinal degeneration occurring in natural and experimental CJD and in some forms of human retinal degeneration have recently been reported. In the present paper a family from an areal focal accumulation of CJD in Central Slovakia with 1 histopathologically verified case of Creutzfeldt-Jakob disease and 2 case of retinitis pigmentosa is described. Neuropathological and epidemiological data obtained in investigated patients are discussed from the point of view of a possible relationship between the slow virus infections caused by unconventional agents and degenerative disease affecting the ocular system.     

中医药治疗原发性视网膜色素变性的临床观察

目的观察中医药治疗原发性视网膜色素变性的临床疗效。方法采用补肾养血明目汤加减,静脉滴注舒血宁和生脉注射液,口服银杏叶片、生脉颗粒及针灸等综合治疗视网膜色素变性64例（128只眼）。结果好转63只眼,无效65只眼,有效率为49%。结论中医药治疗原发性视网膜色素变性是有效的方法。     

视网膜色素变性发病机制及治疗进展

视网膜色素变性（retintis pigmentosa,RP）是指以进行性感光细胞及色素上皮功能丧失为共同表现的遗传性、退行性的疾病,RP是主要的致盲性眼病。其遗传方式包括X连锁遗传、常染色体隐性或者显性遗传,也有散发。临床表现为典型的三联征:骨细胞样色素沉着、视网膜血管缩窄和视盘蜡样苍白。RP具有高度的基因异质性(多个突变位点引起同一疾病）及表型异质性。本文对RP的发病机制和治疗方法进行简要综述。     

中国X连锁视网膜色素变性家系RPGR新突变

目的 检测分析被诊断为X连锁视网膜色素变性（XLRP）的三个中国家系内的基因突变。设计 基因研究。研究对象 三个中国XLRP家系共27位受试者（其中18人为男性）。方法 由同一医生收集家系成员的详细临床资料并进行眼部检查，采集三个家系的先证者及有条件采血者的外周静脉血，提取基因组DNA。应用PCR技术扩增RPGR和RP2基因的全部外显子和内含子交界区序列，包括RPGR基因15号外显子开放阅读框，产物直接测序进行突变分析。主要指标 临床特征及基因测序结果。结果 基因筛查证实了两个RPGR基因的新型无义突变(c.1541C>G;p.S514X 和 c.2833G>T;p.E945X) 及一个错义突变(c.607G>C;p.A203P)。基因型-表型的相关性分析表明家系3患者在接近ORF15下游位置存在突变，这种突变导致视锥细胞功能的早期丧失。ORF15无义突变的女性携带者临床表型重，呈现出部分显性遗传的特点。结论 本研究证实了三种RPGR基因的新型突变，这一结果扩展了RPGR的突变谱及表型谱。     

SD-OCT对原发性视网膜色素变性并发白内障患者行超声乳化联合人工晶状体植入术后视力预后的评估作用

目的　分析原发性视网膜色素变性（retinitis pigmentosa,RP）患者并发白内障行超声乳化联合人工晶状体植入术后视力的影响因素并探讨频域光学相干断层扫描（spectral domain optical coherence tomography,SD-OCT）在评估视力预后中的作用。方法　回顾性系列病例研究。收集RP并发白内障患者38例（58眼）,均行白内障手术治疗。根据SD-OCT下黄斑区椭圆体带的形态将患者分为3组,A组:黄斑区椭圆体带缺失（19眼）,B组:黄斑区椭圆体带可见但不连续（18眼）,C组:黄斑区椭圆体带完整（21眼）。比较所有患者手术前后最佳矫正视力（best corrected visual acuity,BCVA)、组内手术前后BCVA和组间手术前后BCVA;利用Pearson相关分析,分析SD-OCT检测指标的临床意义;并进一步对术后BCVA与黄斑中心凹厚度之间关系进行分析。结果　逐步回归分析结果表明,术前BCVA和黄斑区椭圆体带长度是影响术后视力的主要因素。手术前后BCVA之间、术后BCVA与黄斑区椭圆体带长度之间均呈直线相关（r=0.855、-0.622,均为P<0.01）。A组、B组和C组术前BCVA分别为（2.41±1.05）logMAR、（1.17±0.64）logMAR和（0.83±0.59）logMAR,术后第1天BCVA分别为（1.16±0.90）logMAR、（0.52±0.27）logMAR和（0.21±0.19）logMAR。各组患眼术后第1天BCVA均好于其术前视力（t=5.246、4.632、6.198,均为P<0.01）。3组患眼术后第1天BCVA比较,差异有统计学意义（F=32.760,P<0.01）。A组、B组和C组黄斑区椭圆体带长度分别为（0.00±0.00）mm、（1.16±0.57）mm和（4.04±1.26）mm,黄斑中心凹厚度分别为（100.84±45.49）μm、（203.44±33.33）μm和（248.19±37.79）μm。术后BCVA与黄斑中心凹厚度之间呈直线正相关（r=-0.754,P<0.01）。结论　白内障超声乳化吸出联合人工晶状体植入术治疗RP并发白内障可有效改善视功能。术前视力差、黄斑区椭圆体带结构的破坏以及黄斑中心凹厚度变薄是患者手术后视力不良的指征,SD-OCT对评估视力预后具有一定临床意义。     

硫酸软骨素蛋白多糖在视网膜变性大鼠中的表达

目的 研究硫酸软骨素蛋白多糖(CSPGs)在碘酸钠(NaIO3)诱导的视网膜色素上皮(RPE)细胞变性大鼠中的表达情况.方法 实验研究.24只Sprauge-Dawley(SD)大鼠随机分为4组,正常对照组、造模7d组、造模14 d组、造模28 d组,每组6只.造模组腹腔注射3％ NaIO3(100 mg/kg);取眼球做病理检查,苏木素-伊红(HE)染色及细胞凋亡检测,验证视网膜变性动物模型的建立;免疫荧光法观察视网膜变性大鼠视网膜上CSPGs表达的时空规律;逆转录-聚合酶链反应(RT-PCR)法检测CSPGs多功能蛋白聚糖(Versican) mRNA的表达情况;免疫组织化学法观察视网膜上小胶质细胞表达的巨噬细胞特异性抗原CD68的分布特点.多组比较采用单因素方差分析,两样本间比较采用独立样本t检验.结果 注射NaIO3后,模型大鼠视网膜出现变性改变,且光感受器发牛渐进性凋亡,造模7、14、28 d组凋亡率分别为(21.0±3.5)％、(32.3±2.3)％、(41.7±2.6)％,各组间差异有统计学意义(F=205.27,P＜0.01).造模7d组,CS-56、CD68在脉络膜、视锥视杆层、内核层、节细胞层表达;造模14 d组,CS-56、CD68进一步出现在外核层;造模28 d组,CSPGs继续迁移到外丛状层.随造模时间延长,各层荧光表达逐渐增强,CD68在视网膜各层的表达也明显增多,强度分别为:1.33±0.52、2.67±0.82、4.00±1.10和7.17±1.33,各组间差异有统计学意义(F=38.45,P＜0.01).造模组Versican mRNA表达(1.02±0.06)显著高于正常对照组(0.23±0.02),差异有统计学意义(t=-26.05,P＜0.01).结论 在碘酸钠诱导的视网膜变性动物模型中,随时间延长CSPGs表达范围扩大,表达量增加,并与小胶质细胞分布在大致相同区域,提示CSPGs可能来源于小胶质细胞.