兔胚胎全层视网膜移植至大鼠视网膜下的观察

视网膜色素变性(RP)是一组能导致进行性感光细胞变性和视觉障碍的遗传病症候群，目前尚无有效治疗方法。近年来研究表明视网膜移植是最接近临床应用治疗RP的方法。当RP进展到晚期，感光细胞和视网膜色素上皮(RPE)细胞都出现变性死亡，单独移植这两种成分都没有作用，此时病变视网膜的修复需要全层视网膜的移植。我们将青紫蓝兔胚胎全层视网膜移植到正常Wistar大鼠和视网膜变性RCS大鼠的视网膜下腔，观察移植物在宿主视网膜下腔的发育状况，从而探讨异种胚胎全层视网膜移植方法的可行性。     

脑源性神经营养因子治疗视网膜色素变性的研究进展

脑源性神经营养因子(BDNF)是一种由脑组织合成并广泛分布于中枢神经系统的小分子碱性蛋白.研究发现,BDNF对视网膜神经节细胞(RGCs)、视网膜感光细胞(RPCs)和视网膜色素上皮(RPE)细胞均有保护、营养及抗凋亡作用.视网膜色素变性(RP)是由于RPCs及RPE细胞凋亡引起的视网膜退行性疾病.RP动物模型证实了BDNF的长期给药对于RP的治疗价值.然而BDNF在体内的半衰期较短,且无法跨越血-视网膜屏障由循环系统输送到视网膜,这给BDNF用于RP的治疗带来了挑战.为了使BDNF在眼内可以稳定持续地释放,多种新型给药方式已被尝试,包括基因工程技术、细胞移植技术、高分子材料缓释系统及滴眼液等.本文就BDNF对RP治疗的研究现状及BDNF的新型给药方式做一综述.     

视网膜色素变性新疗法的评估

视网膜色素变性 (RP)是一种眼科常见的遗传性疾病 ,预后往往不佳。近年来 ,随着基因治疗、视网膜移植、神经远祖细胞移植、视网膜细胞营救等技术的广泛开展和完善 ,给RP病的治疗带来了新的希望。本文现就RP病治疗的研究现状和前景 ,以及各种方法的特点做一理论分析     

视网膜色素变性治疗最新进展

视网膜色素变性(retinitis pigmentosa,RP)是视网膜感光细胞和色素上皮细胞变性导致的最常见遗传性致盲眼病,预后不佳,目前尚无有效的预防和治愈方法。近年来,随着基因治疗、视网膜移植等技术在动物实验中的广泛开展,给人类RP的治疗带来了新的希望。本文对RP的各种最新治疗进展进行综述。     

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。     

视网膜移植治疗视网膜色素变性的研究进展

视网膜色素变性 (RP)是一种遗传性眼病 ,目前尚无切实有效的治疗方法 ,视网膜移植是最有前景的治疗措施。本文就视网膜移植治疗视网膜色素变性的方法学、免疫学、解剖学及临床研究进展作一综述     

原发性视网膜色素变性的治疗研究进展

原发性视网膜色素变性 (retinitispigmentosa ,RP)是常见的单基因遗传性疾病 ,通常双眼发病 ,最终可导致患者失明。近几年 ,RP治疗的实验研究取得相当大的进展 ,基因治疗、生长因子治疗、视网膜移植和人工视网膜等都有所突破 ,后两者已用于人体试验。此外 ,对经典的药物疗法以及传统医学治疗方面也进行了新的探索。     

视网膜色素变性的治疗进展

视网膜色素变性(RP)是一组以进行性感光细胞及色素上皮细胞功能丧失为共同表现的遗传性视网膜疾病.临床表现为夜盲,伴有进行性视野缺损,眼底色素沉着和视网膜电流图异常.近年对该病治疗上有一些研究.文中介绍了应用基因治疗、细胞移植、药物、人工视觉等方面治疗RP的一些进展.     

视网膜色素变性的眼底血流变化研究现状

视网膜色素变性(retinitis pigmentosa,RP)是一种临床常见的遗传性致盲性眼底病,多由夜盲起病,经过几十年进行性视力下降致最终失明.其病理特点为原发性感光细胞凋亡长期发展最终导致视网膜色素上皮和内层视网膜结构及功能损伤.多个研究表明RP早期出现眼底血流减少.原因可能是原发性血管功能失调和血浆内皮素-1升高.目前有多种可有效评估视网膜血流情况的方法.针对改善眼底血流的治疗能够在一定程度上延缓RP病情的进展.对于眼底血流和RP关系的认识加深有助于寻找新的有效治疗RP的方法.     

New drug therapy for retinal degeneration

Retinitis pigmentosa (RP) is an inherited retinal degeneration characterized by nyctalopia, ring scotoma, and bone-spicule pigmentation of the retina. So far, no effective therapy has been found for RP. As a possible molecular etiology of RP, retina-specific gene deficits are most likely involved, but little has been identified in terms of intracellular mechanisms leading to retinal photoreceptor cell death at post-translational levels. In order to find an effective therapy for RP, we must look for underlying common mechanisms that are responsible for the development of RP, instead of designing a specific therapy for each of the RP types with different causes. Therefore, in the present study, several animal models with different causes of RP were studied, including (1)Royal College of Surgeons (RCS) rats with a deficit of retinal pigment epithelium (RPE) function caused by rhodopsin mutation; (2) P23H rats, (3) S334ter rats, (4) photo stress rats, (5) retinal degeneration (rd) mice with a deficit of phosphodiesterase(PDE) function; and (6) cancer-associated retinopathy (CAR) model rats with a deficit of recoverin-dependent photoreceptor adaptation function. In each of these models, the following assessments were made in order to elucidate common pathological mechanisms among the models: (1) retinal function assessed by electroretinogram (ERG), (2) retinal morphology, (3) retinoid analysis, (4) rhodopsin regeneration, (5) rhodopsin phosphorylation and dephosphorylation, and (6) cytosolic cGMP levels. We found that unregulated photoreceptor adaptation processes caused by an imbalance of rhodopsin phosphorylation and dephosphorylation caused retinal dysfunction leading to photoreceptor cell death. As possible candidate drugs for normalizing these retinal dysfunctions and stopping further retinal degeneration, nilvadipine, a Ca channel blocker, retinoid derivatives, and anthocyanine were chosen and tested to determine their effect on the above animal models with retinal degeneration. Nilvadipine showed beneficial effects against retinal degeneration in all models tested, but retinoid derivatives and anthocyanine showed these beneficial effects in only some models. Thus our present data allowed us to test the effectiveness of nilvadipine in the treatment of human RP patients.     

Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives

Retinitis Pigmentosa (RP) is a hereditary retinopathy that affects about 2.5 million people worldwide. It is characterized with progressive loss of rods and cones and causes severe visual dysfunction and eventual blindness in bilateral eyes. In addition to more than 3000 genetic mutations from about 70 genes, a wide genetic overlap with other types of retinal dystrophies has been reported with RP. This diversity of genetic pathophysiology makes treatment extremely challenging. Although therapeutic attempts have been made using various pharmacologic agents (neurotrophic factors, antioxidants, and anti-apoptotic agents), most are not targeted to the fundamental cause of RP, and their clinical efficacy has not been clearly proven. Current therapies for RP in ongoing or completed clinical trials include gene therapy, cell therapy, and retinal prostheses. Gene therapy, a strategy to correct the genetic defects using viral or non-viral vectors, has the potential to achieve definitive treatment by replacing or silencing a causative gene. Among many clinical trials of gene therapy for hereditary retinal diseases, a phase 3 clinical trial of voretigene neparvovec (AAV2-hRPE65v2, Luxturna) recently showed significant efficacy for RPE65-mediated inherited retinal dystrophy including Leber congenital amaurosis and RP. It is about to be approved as the first ocular gene therapy biologic product. Despite current limitations such as limited target genes and indicated patients, modest efficacy, and the invasive administration method, development in gene editing technology and novel gene delivery carriers make gene therapy a promising therapeutic modality for RP and other hereditary retinal dystrophies in the future.     

Therapeutic strategies in RP (retinitis pigmentosa): light at the end of the tunnel?

Retinitis pigmentosa (RP) is a hereditary retinal dystrophy which leads to severe visual impairment or blindness and affects about 3.5/1000 of individuals in the industrial world. During the past decades, numerous animal models carrying mutations analogous to mutations in human RP have been studied to elucidate the molecular mechanisms leading to apoptotic photoreceptor cell death in this disease. Up to date, there is no effective treatment to influence the fatal outcome of RP. Recent progress in basic research promotes the development of new therapeutic strategies. In order to restore visual function in blind individuals, the development of electronic photoreceptor prosthesis is being investigated by several researchgroups. Other promising approaches are somatic gene therapy, the application of growth factors and/or pharmacological agents and the inhibition of photoreceptor cell death by interfering with the apoptotic pathway. However, a better understanding of the molecular events leading to cell loss due to photoreceptor apoptosis will be essential for the development of effective treatment.     

碘酸钠诱发的视网膜色素变性动物模型研究进展

视网膜色素变性(RP)是一组以视网膜色素上皮(RPE)和感光细胞的功能障碍或丧失为主要特征的致盲眼病,有很大的临床和遗传异质性.碘酸钠是抗代谢药物,可以选择性破坏RPE,它引起的视网膜病变与人类RP疾病的片状RPE缺损极为相似,因此常被用来制作RP疾病的模型.碘酸钠能诱发多种实验动物的RP模型,人们多使用单次碘酸钠注射的方法建立RP动物模型.由于碘酸钠诱发的RP动物模型的发病年龄和疾病进展均可人为操控,制备简单,病变稳定,周期短,且某些动物的RPE细胞在特殊条件下有再生的潜能,极有利于RP发病机制、药物或干/前体细胞治疗及再生医学方面的研究.目前有关碘酸钠诱发动物RP模型的研究和应用已有不少报道.本文根据国内外文献将碘酸钠诱发的RP动物模型的研究进展作一综述.     

用科学的态度正确认识视网膜色素变性

视网膜色素变性(RP)是最常见的遗传性致盲眼底病,具有高散发性和高临床异质性.除了常见的遗传类型外,还具有双基因遗传,线粒体遗传,不完全显性遗传等新遗传方式.RP的表型复杂,Peripherin/RDS、RHO、RP2和RP3等RP基因出现了基因型和表型不一致现象,中心性、单发性、无色素性和缓慢型视网膜变性等少见RP具有复杂的临床表型.视网膜移植术、视网膜植入术、药物及神经营养因子治疗和基因治疗等治疗体系已经建立.但是,一些眼科医师对于RP治疗的新进展和新知识了解不多,因此积极地更新知识,以科学的态度正确地认识RP非常必要.(中华眼科杂志,2009,45:193-195)     

Review and update: Current treatment trends for patients with retinitis pigmentosa

BackgroundRetinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders characterized by progressive photoreceptor apoptosis. It is the leading cause of inherited retinal degeneration–associated blindness. RP has a unique set of clinical characteristics that make it a complex disease associated with distinct inheritance patterns. An understanding of the pathogenesis is essential in the process of the differential diagnosis and the development of treatment options. Recent developments in research are likely to expand the various therapeutic modalities to include gene therapy, pharmacologic treatment, cell transplantation, and neuro-prosthetic devices.MethodsA literature search was performed to comprehensively review RP diagnosis, pathophysiology, and treatment.ConclusionAdvances in the understanding of the pathophysiology of RP are creating new opportunities for the treatment of this often visually debilitating eye condition. Optometrists, as primary eye care practitioners, should be aware of the inheritance, pathophysiology, and current treatment options for RP as well as treatments in development so that they can best care for their patients with inherited retinal disorders.