常染色体显性遗传视网膜色素变性致病基因的研究进展

视网膜色素变性（retinitis pigmentosa,RP)是常见的遗传性视网膜变性疾病，它具有高度的遗传异质性，有不同的遗传方式和临床表型，目前已发现常染色体显性遗传型视网膜色素变性（autosomal dominant retinitis pigmentosa,ADRP)的12种基因，其中已被克隆的有RHO，RDS，ROM1，RP1，NRL及CRX，未被克隆的有RP9，RP10，RP11，RP13，RP17及RP18，本文主要介绍与ADRP相关的几个基因的最新研究进展。     

X-连锁和双基因型视网膜色素变性的相关基因研究进展

视网膜色素变性（retinitis pigmentosa,RP)是一组进行性、可致盲的单基因遗传性视网膜疾病，以视网膜光感受器和色素上皮功能进行性受损为主要特征。X－连锁RP和双基因型RP是视网膜色素变性的不同类型，在遗传和临床上各具特点。目前，X－连锁RP已定位6个致病基因，并克隆了2个基因（RP2和RP3）；双基因型RP是由2种不同基因（peripherin/RDS和ROM1基因）的杂合子突变导致的。     

基于RCS大鼠模型的视网膜色素变性治疗

视网膜色素变性是一类以光感受器细胞及色素上皮细胞功能丧失为共同表现的疾病,具有遗传倾向性,通过选择不同的视网膜色素变性(relinitis pigmentosa,RP)动物模型可以针对不同遗传方式的RP进行研究,皇家外科学院(royal college surgeons,RCS)大鼠是常染色体隐性遗传的经典动物模型,现将基于RCS大鼠模型的RP治疗研究进展综述如下.     

视网膜色素变性基因治疗的相关研究进展

视网膜色素变性(RP)是以视杆和视锥感光细胞退化及视网膜色素上皮细胞变性为特征的遗传性视网膜疾病。RP发病年龄和病情进展与基因和遗传方式有关，受环境影响。基因治疗通过载体转移治疗性基因，对靶细胞进行遗传修饰，纠正或替代致病RP基因。本文介绍RP基因治疗相关基因载体研究进展，并就5个常见基因型(RHO、PDE6B、MERTK、RLBP1、RPGR)对RP基因治疗疗效及安全性研究进展予以综述。     

视网膜色素变性治疗的研究进展

视网膜色素变性(retinitis pigmentosa,RP)是由视网膜光感受器和视网膜色素上皮变性所引起的致盲性、遗传性眼病,目前尚无有效的治疗方法,相关治疗研究还处于探索阶段,如基因治疗、药物治疗、移植治疗、人工视网膜假体等。基因治疗RP是目前的研究热点,包括修复致病基因、核酸治疗、RNA干扰技术等。基因治疗、干细胞移植、人工视网膜假体治疗RP已经进入临床试验阶段,为治疗该病带来了新的希望。本文就RP治疗的研究进展做一综述。     

视网膜色素变性治疗研究进展

视网膜色素变性(retinitis pigmentosa,RP)是一组遗传性视网膜疾病,其特征是渐进性感光细胞和视网膜色素上皮(RPE)细胞功能障碍,是世界范围内常见的致盲性眼病,且缺乏有效的治疗方法。目前RP的治疗方法包括干细胞治疗、基因治疗、神经保护治疗、营养疗法、高压氧疗法、视网膜移植和中医治疗。本文综述了近年来国内外有关RP治疗的研究进展。     

Coats型视网膜色素变性

Coats型视网膜色素变性(Coats-type retinitis pigmentosa,简称Coats型RP),即视网膜毛细血管扩张症和/或渗出性视网膜脱离。本病与典型的Coats病有本质的区别,与视网膜色素变性有某种关系,在视网膜色素     

视网膜色素变性的免疫学研究

视网膜色素变性(retinitis pigmentosa,RP)是一原因尚未明了的,具有遗传倾向的慢性进行性视网膜色素上皮的变性性疾病。典型特征是:夜盲、中心视力损害,周边视野缺损或环形暗点形成,视网膜骨细胞样色素沉着,视网膜电图异常或熄灭。近来,多数学者应用免疫学的方法探索和研究RP的病因及发病机理。笔者复习了近年RP免疫学研究的有关资料,现作一综述。     

视网膜色素上皮细胞吞噬功能与信号转导系统的关系

视网膜色素变性(RP)是一种严重的致盲性眼病,其确切病因不明。除了遗传因素外,近年的研究表明,视网膜色素上皮(RPE)细胞吞噬功能异常是导致视觉功能障碍的主要原因。本文简单介绍视网膜色素上皮细胞特异性吞噬功能,详细分析了IP3、PKC、cAMP、cGMP、PTK及Ca2+对RPE细胞吞噬的调节作用,综述了RP发病机制中涉及RPE细胞吞噬功能与信号转导系统的研究进展。     

第六届视网膜色素变性国际会议综述

第六届视网膜色素变性国际会议于1990年7月19～22日在爱尔兰都柏林大学召开。这次盛会充分反映了近2年来世界各国对视网膜色素变性(RP)及其它变性视网膜疾病的基础和临床研究的动态和最新进展。内容包括各遗传型RP的基因定位、RP患者视紫红质基因点突变的研究、性连锁遗传型RP和无脉络膜病的基因克隆;RP动物模型发病机理的生化研究及分子遗传学研究;RP的基因治疗与细胞移植的实验研究;Refsum综合征患者的生化缺陷和临床治疗;以及RP的其它临床问题等。本文对这些内容进行了简要综述。     

常染色体隐性遗传视网膜色素变性的相关基因研究进展

视网膜色素变性(rentinitis pigmentosa，RP)是一种发病机制尚未完全明确的遗传性致盲性视网膜疾病，特征性表现为夜盲、进行性视野缩窄和视力下降，眼底可见骨细胞样色素沉着、视网膜血管变细和视盘蜡黄三联症。RP具有较大的遗传异质性和临床异质性，其中常染色体隐性遗传视网膜色素变性(autosomal recessive RP，ARRP)占RP的5%～20%，目前已定位43个致病基因，克隆了其中40个，并且不断有新的相关致病基因被报道。本文就近3a发现与ARRP相关的AGBL5、ARHGEF18、HGSNAT和ZNF408四个基因研究进展作一综述。     

Sector retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) is one of the most common hereditary retinal dystrophies and causes of visual impairment affecting all age groups. The reported incidence varies, but is considered to be between 1 in 3,000 to 1 in 7,000. Sector retinitis pigmentosa is an atypical form of RP that is characterized by regionalized areas of bone spicule pigmentation, usually in the inferior quadrants of the retina. CASE REPORT: A 57-year-old Hispanic man with a history of previously diagnosed retinitis pigmentosa came to the clinic with a longstanding symptom of decreased vision at night. Bone spicule pigmentation was found in the nasal and inferior quadrants in each eye. He demonstrated superior and temporal visual-field loss corresponding to the areas of the affected retina. Clinical measurements of visual-field loss, best-corrected visual acuity, and ophthalmoscopic appearance have remained stable during the five years the patient has been followed. DISCUSSION: Sector retinitis pigmentosa is an atypical form of RP that is characterized by bilateral pigmentary retinopathy, usually isolated to the inferior quadrants. The remainder of the retina appears clinically normal, although studies have found functional abnormalities in these areas as well. Sector RP is generally considered a stationary to slowly progressive disease, with subnormal electro-retinogram findings and visual-field defects corresponding to the involved retinal sectors. CONCLUSION: Management of RP is very difficult because there are no proven methods of treatment. Studies have shown 15,000 IU of vitamin A palmitate per day may slow the progression, though this result is controversial. Low vision rehabilitation, long wavelength pass filters, and pedigree counseling remain the mainstay of management.     

Cataract in retinitis pigmentosa. An analysis of cataract surgery results and pathological lens changes

The result of cataract surgery and lens pathoanatomical examination were presented in patients with retinitis pigmentosa (RP). A retrospective study of 24 cataract extractions in 15 RP patients was carried out, with special regard to visual outcome and surgical complications. The results were compared to an age matched randomly selected control group. In the retinitis pigmentosa group the post-operative visual acuity was generally good, and the surgical complications except for one case of central venous thrombosis were not more frequent than in the control group. Seven lenses from 5 patients with RP were analysed using transmission electron microscopy and quantitative microradiography. In the lenses with a progressive subcapsular edema, extensive extracellular vacuolization was found in the lens epithelium. Focal degeneration of epithelial cells was seen both in the more stationary posterior subcapsular cataracts and the progressive subcapsular cataracts. Different degrees of mitochondrial swelling was found in the epithelial cells of the stationary cataracts. The subcapsular lens fiber changes consisted of an extensive swelling of hydrated cells together with a significant reduction in their dry mass content. Migrating elongated nuclei-containing cells were found on the posterior capsule in both stationary and progressive cataracts.     

Novel mutation in RP2 gene in two brothers with X-linked retinitis pigmentosa and mtDNA mutation of leber hereditary optic neuropathy who showed marked differences in clinical severity

PURPOSE: To report the identification of a novel mutation of the RP2 gene in two Japanese brothers with X-linked retinitis pigmentosa of a differing clinical severity. The mother was a carrier of both retinitis pigmentosa and optic atrophy. METHODS: The older brother had a severe form of retinitis pigmentosa associated with macular degeneration and total optic atrophy, whereas the younger brother presented typical X-linked retinitis pigmentosa. RESULTS: Each patient exhibited a novel 2-bp insertion at codon 278 in exon 3 of the RP2 gene as well as a 11778 mutation in mitochondrial DNA. This suggests that the older brother may have developed Leber hereditary optic neuropathy as well as retinitis pigmentosa. CONCLUSION: Molecular testing confirmed the clinical diagnosis in each case. However, such testing did not explain the differences in the severity of the ophthalmoscopic findings between the two brothers.     

A new Leu253Arg mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa

PURPOSE: To identify the clinical findings in a Japanese family with X-linked retinitis pigmentosa associated with mutation in codon 253 (Leu253Arg) in the RP2 gene. METHODS: Case reports included clinical features and results of fluorescein angiography, electroretinogram, kinetic visual field testing, and DNA analysis. Two affected hemizygotes with retinitis pigmentosa associated with transversion mutations in codon 253 (Leu253Arg) of the RP2 gene and the obligate carriers were examined. RESULTS: A novel Leu253Arg mutation of the RP2 gene was found to cosegregate with retinal degeneration in two affected males and two carriers in female heterozygote in a Japanese family. The ophthalmic findings in hemizygote showed severe retinal degeneration. In the obligate carrier, mild chorioretinal degeneration was observed in both eyes but a tapetal-like reflex of the fundus was not apparent. CONCLUSIONS: The mutation at codon 253 of the RP2 gene is the first mutation reported in a Japanese family. It is concluded that the mutation of the RP2 gene also causes the X-linked retinitis pigmentosa in Japanese patients.     

Metabolic monitoring of transcorneal electrical stimulation in retinitis pigmentosa

Graefe's Archive for Clinical and Experimental Ophthalmology - Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). With...     

INVESTIGATION OF RETINITIS PIGMENTOSA

Retinitis pigmentosa is a solitary manifestation o1 separate genetically determined disorders in which there is progressive loss of vision and the appearance of characteristic fundus abnormalities. It is likely that each disease contained within this family of disorders has a different aetiology, a consideration which is important to the clinician, the researcher and the therapist. To the clinician it is essential to be able to identify the inheritance of the disorder in order to give educated genetic advice. It is the responsibility of the clinician to sub-divide retinitis pigmentosa into purer samples of disease since without such a sub-division research is unlikely to be fruitful. It is unreasonable to expect a biochemist to define systemic biochemical abnormalities if blood is analysed from a series of patients, each of which has a different disorder. If the cause of retinal degeneration in an animal homologue of human retinitis pigmentosa is identified the question is then raised as to whether the abnormality is relevant to human disease and, if so, to which one. Moreover, if a metabolic abnormality is identified in one disease it will not necessarily be found in others and similarly, if therapy is effective in one form of the disease it may not be effective for all patients. A sub-division of retinitis pigmentosa may be made on the basis of inheritance of the disorder, on the basis of morphologic changes in the fundus, and on the qualitative functional changes identified. Such observations may also give some clues as to the pathogenesis of the different forms of RP or at least indicate in which cell system the primary disorders lie and will also show in what way the defect interferes with cell function. In this paper it is hoped to show that studies undertaken by the various disciplines within ophthalmology have now made limited achievements towards the goals of subdividing retinitis pigmentosa (RP) into purer samples of disease and typifying the functional and morphological attributes of the constituent disorders.     

视网膜色素变性遗传致病基因peripherin/RDS的突变筛选

目的 了解中国视网膜色素变性患者（RP）中peripherin/RDS基因的突变谱及突变率。方法 应用聚合酶链-异源双链-单链构象多态性（PCR-SSCP）及DNA序列分析技术对收集的15个常染色体显性遗传视网膜色谱变性家系和55例散发视网膜色素变性患者peripherin/RDS基因的第一，第二外显子进行检测。结果 15个家系及55例散发患者未检测到peripherin/RDS基因突变。结论 本研究所检测的视网膜色素变性患者与RDS基因无关，显示视网膜色素变性的遗传异质性。     

中国人与欧美人USH2A基因突变谱不同

Usher综合征是一种常见的综合征性视网膜色素变性（RP）,为常染色体隐性遗传性疾病,具有临床和遗传高度异质性。迄今已将Usher综合征的致病基因定位了12个染色体位点,确定了其中的9个致病基因。很多研究证实USH2A基因是Usher综合征的主要致病基因,USH2A基因突变还可引起单纯性RP,但国内的一些研究结果发现,中国人USH2A基因突变谱与欧美人不同。中国人RP致病的热点基因谱尚有待进一步研究。     

视网膜色素变性1基因在常染色体显性遗传视网膜色素变性家系中的突变分析

目的:研究常染色体显性遗传视网膜色素变性(autosomal dominant retinitis pigmentosa,ADRP)家系中视网膜色素变性1(retinitis pigmentosa-1,RP1)基因的突变特征及其在RP发病机制中的作用。方法:运用聚合酶链反应和直接测序方法,对6个ADRP家系的47例成员和50例对照者进行了RP1基因全编码区和邻近剪切位点的内含子区域序列突变的筛选与检测。运用单因素分析、多因素Logistic回归分析研究RP1基因点突变在RP发病中的作用。结果:ADRP家系成员和对照组RP1基因第4外显子上检测出2个变异位点。在1691和1725密码子存在杂合的两种类型的密码子(S1691P,Ser-Pro,TCT→CCT;Q1725Q,Gln-Gln,CAA→CAG)。ADRP家系成员中Ser-1691-Pro及Gln-1725-Gln位点突变率显著高于正常对照组(χ2=11.202,P<0.05)。结论:RP1基因Ser-1691-Pro及Gln-1725-Gln位点多态性可增高RP的危险性,具有潜在的致病性,考虑为ADRP家系的易感基因。