微小RNA在视网膜疾病中表达及功能的研究进展

微小RNA(miRNA)是一类内源性、非编码单链RNA,长度约为22个核苷酸,他们通过与靶mRNA的3’端非编码区结合来抑制基因的表达,参与调节组织器官的生长发育、分化、功能维持和凋亡等重要的生理过程.miRNA是近年来生命科学领域中的研究热点,越来越多的研究表明多种miRNA在眼部表达,其中超过250种miRNA在视网膜组织中表达并影响其生长、发育和功能.本文就近年来miRNA在视网膜疾病的表达及功能作一综述.     

微小RNA与年龄相关性黄斑变性发病的关系

微小RNA (miRNA)是指一种小的内源性非编码RNA分子,其异常表达与年龄相关性黄斑变性(age-related macular degeneration,AMD)发生发展密切相关.miRNA在AMD的炎性反应、氧化应激损伤、淀粉样蛋白及脉络膜新生血管形成等病变过程中贯穿始终.这些发现可能为AMD的早期诊断、治疗及预后判断提供新的可能性.     

微小RNA与视网膜发育相关性研究进展

微小RNA(miRNA)是相对分子质量较小、性质稳定的RNA,通过与目的mRNA的部分互补序列碱基互补配对而在转录后水平调节动物、植物的基因表达及抑制蛋白质合成.目前发现在视网膜中表达的miRNA有200多种,miRNA对基因的表达调控影响了视网膜的正常发育,与神经视网膜的发生、视网膜光感受器的分型及正常数量维持、神经节细胞的存活及轴突生长、视网膜色素上皮层的发育均有密切联系.此外,miRNA的调控还与视网膜损伤后的再生有关.miRNA对视网膜发育的调控主要通过直接靶向调节与此有关的某些目的基因的表达,或通过调节某些信号通路组分来实现,在视网膜发育过程中,miRNA功能的正常发挥为视网膜正常形态结构的形成提供了保障,从而为其发挥正常的生理功能提供了物质基础.现就脊椎动物视网膜中miRNA的生物学功能与视网膜发育的相关性研究进展进行综述.     

微小RNA在糖尿病视网膜病变新生血管生成中的研究进展

微小RNA(miRNA)是一类内生的、长度约20 ～ 24个核苷酸的具有组织特异性和高度保守的RNA,通过与mRNA互补配对在转录后水平降解mRNA或抑制mRNA翻译来负调控靶基因的表达.多项研究已表明miRNA的亚型基因miR-126、miR-31、miR-200b和miR-29等在一定程度上与糖尿病视网膜病变(DR)的新生血管生成有关,通过一系列调控血管内皮生长因子(VEGF)的表达,进而抑制或促进血管新生,而VEGF是一种新生血管的主要促进因子,能够特异性的刺激血管内皮细胞的增生及新生血管生成,破坏血-视网膜屏障,加快DR的进展.因此,揭示miRNA在DR新生血管形成中的作用及其机制是未来DR机制研究的重要方向,并可为DR的防治提供新的策略.现就miRNA在DR新生血管形成的研究进展作一综述.     

RNA干扰技术在视网膜疾病治疗中的研究进展

RNA干扰(RNA interference,RNAi)是一种在动物中广泛存在的、通过双链RNA分子在mRNA水平上诱导特异性序列基因沉默的过程。作为一种阻断基因表达的新手段,RNAi技术日趋成熟完善,开辟了一条基因治疗的新途径。RNAi技术能够有效阻止视网膜新生血管的形成,抑制增生性玻璃体视网膜病变的发生和发展,诱导视网膜母细胞瘤细胞的凋亡。现将RNAi技术在上述视网膜病变中的研究进展作一综述。     

程序性坏死与视网膜疾病相关性的研究进展

程序性坏死是由分子受体相互作用蛋白激酶1、分子受体相互作用蛋白激酶3和混合系激酶区域蛋白介导的一种不同于凋亡及传统坏死的细胞程序性死亡方式,可由肿瘤坏死因子受体或模式识别受体调控启动。越来越多的研究发现,程序性坏死在视网膜疾病发生和发展中起关键作用。本文将对程序性坏死的分子机制及程序性坏死与视网膜疾病相关性的研究进展进行综述,以帮助寻找治疗视网膜疾病的新靶点。     

survivin在视网膜新生血管中的表达及其与VEGF的相关性研究

本研究通过高氧诱导的视网膜新生血管模型，观察survivin在视网膜新生血管中的表达，并探讨其与血管内皮生长因子（vasculur endothelial growth factor,VEGF）之间的关系。     

VEGF抑制剂在眼内新生血管疾病中的应用

眼内新生血管形成是老年黄斑变性、糖尿病视网膜病变、视网膜静脉阻塞、新生血管性青光眼等疾病共有的病理改变。其相伴的渗出、出血、增生等一系列病理改变可严重破坏眼的结构和功能，导致患者不同程度的视力障碍。研究证实血管内皮生长因子（VEGF）在新生血管形成过程中起关键性刺激作用。     

环状RNA在眼科疾病中的作用

环状RNA(circRNA)是由前体mRNA反向剪接形成的具有封闭结构的环状分子,可充当微小RNA(miRNA)"海绵",与蛋白质、RNA结合形成复合物,发挥调控宿主基因表达、蛋白翻译的功能,在生理学和病理生理学中具有重要意义。多种眼科疾病中均存在特异性circRNA的异常表达,其通过"海绵"作用调控靶基因表达可引起多...     

A common microRNA signature in mouse models of retinal degeneration

Perturbed microRNA (miR) expression is a feature of, and may play a fundamental role in, certain disease states such as different forms of cancer. Retinitis pigmentosa (RP) a group of inherited retinal degenerations is characterised by a progressive loss of photoreceptor cells and consequent visual handicap. We have previously reported an altered pan-retinal expression of miR-96, -183, -1 and -133 in a P347S-Rhodopsin transgenic mouse model of RP. As many different mutations in Rhodopsin and other genes such as RDS/Peripherin can lead to RP, it was of interest to explore whether the characterized retinal miR expression signature was observed in three other mouse models of RP linked to rhodopsin and rds/peripherin. Therefore, pan-retinal expression of miR-96, -182, -183, -1, -133 and -142 was analysed using quantitative real-time RT-PCR. A common signature of altered miR expression was found; expression of miR-96, -182 and -183 decreased by 14.1-53.2%, while expression of miR-1, -133 and -142 was up-regulated by 186.1-538.5%. Significantly, the detected pan-retinal miR signature was mirrored by similar miR expression profiles in FACS-isolated rod photoreceptors from these mice. In an attempt to understand the function of these miRs, corresponding target genes were predicted using computational means. Many ‘enriched’ targets (with binding sites for at least two of the above miRs) were found to be regulatory molecules and members of intracellular signalling circuits. However, further studies are required to highlight which of the large number of in silico predicted targets are actually controlled by these miRs.     

Retinal histopathology of a carrier of X-chromosome-linked retinitis pigmentosa

Autopsy eyes were examined from a 79-year-old female carrier of X-chromosome-linked retinitis pigmentosa. At age 78 years, she had no visual symptoms but had intraretinal bone spicule pigmentation in the nasal and inferior periphery of both eyes. Rods, cones, and pigment epithelium in the central retina appeared normal. In the midperiphery, patches with advanced photoreceptor cell degeneration were observed overlying pigment epithelium containing melanolysosomes. Within these patches, rods and cones were reduced in number or absent, and pigment epithelial cells abutted the external limiting membrane. A precipitous decline in rod nuclei was observed in transitional zones between areas of apparently normal photoreceptors and areas of absent photoreceptors. In the far periphery, large areas lacked photoreceptors and pigment epithelium. Histopathologic findings in this elderly carrier are compared with those previously described in a 24-year-old man with X-chromosome-linked retinitis pigmentosa.     

Massive peripheral retinal sclerosis

Peripheral retinal sclerosis (PRS) is especially massive in cases of high myopia and retinitis pigmentosa. The distribution and configuration of the sclerotic formations in nine such cases were studied and compared by light microscopy and SEM. Different aspects of the sclerotic structures are described. It is shown that no formations of PRS lie isolated within the degenerated retinal tissue as could be supposed by light microscopy. They are always in multiple contact to or originate from the vitreo-retinal border layer and/or peripheral retinal vessels. This leads to the supposition that these preexisting collagenous structures participate in some way in the formation of PRS.     

Retinal capillaritis in a CRB1-associated retinal dystrophy

Purpose: To report a case of CRB1-associated retinal dystrophy characterized by vitritis, retinal capillaritis, and cystoid macular edema (CME).

Methods: A case report.

Results: An 8-year-old boy was diagnosed with intermediate uveitis and treated with corticosteroids. He was subsequently diagnosed with retinal dystrophy and found to have two CRB1 mutations.

Conclusions: Retinal capillaritis, vitritis, and CME could be inflammatory features of CRB1 retinal dystrophy in our young patient.     

Retinitis pigmentosa and allied diseases: applications of electroretinographic testing

Electroretinograms (ERGs) have provided criteria for establishing the diagnosis of retinitis pigmentosa in early life even at a time when fundus abnormalities visible with the ophthalmoscope are minimal or absent. Patients with widespread progressive forms of retinitis pigmentosa have shown not only reduced amplitudes but also delays in cone or rod b-wave implicit times, or both, while patients with self-limited sector retinitis pigmentosa or stationary forms of night blindness have had reduced amplitudes with normal b-wave implicit times. In families with retinitis pigmentosa ERGs can be used not only to identify which patients are affected but also to establish which patients are normal as those patients, age 6 and over, with normal cone and rod amplitudes and normal cone and rod b-wave implicit times have not been observed to develop primary retinitis pigmentosa at a later time. ERGs from patients with retinitis pigmentosa and allied night blinding disorders are presented to show their usefulness in genetic typing, documenting natural histories, and defining possible pathogenetic mechanisms. The potential application of the ERG in evaluating the efficacy of therapeutic trials is also considered.Presented in part as the Alex E. Krill Memorial Lecture before The Chicago Ophthalmological Society, Chicago, Illinois, October 15, 1979.This research was supported in part by Specialized Research Center Grant EY02014 from the National Institutes of Health and in part by the National Retinitis Pigmentosa Foundation, Baltimore, Maryland and the George Gund Foundation, Cleveland, Ohio, U.S.A.     

小胶质细胞在人原发性视网膜色素变性中的活化

目的 观察小胶质细胞在原发性视网膜色素变性(RP)患者中的活化表现.方法制备22个原发性RP患者及18个正常人眼的石蜡切片.抗体HLA-DR,CD45及CD68对视网膜小胶质细胞进行免疫标记. 结果 RP患者赤道部视网膜内层出现大量肥大的活化小胶质细胞,部分向变性的感光细胞层浸润.黄斑区小胶质细胞主要以三种形式存在:在视网膜内层明显活化并向感光细胞层浸润;在视网膜内层活化但很少向外核层浸润;视网膜全层未见小胶质细胞活化.视神经及视网膜前膜均见小胶质细胞活化.结论小胶质细胞的活化是RP的一种独特的炎性反应方式,在感光细胞变性中发挥一定作用.     

Immune responsiveness to retinal S-antigen and opsin in serpiginous choroiditis and other retinal diseases

The immune responsiveness to bovine retinal S-antigen and opsin has been investigated in some retinal disorders by means of in vitro lymphocyte proliferation, leukocyte migration inhibition and enzyme linked immune sorbent assays (ELISA). Sensitisation to S-antigen was observed in serpiginous choroiditis, but not in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or retinitis pigmentosa. No significant immune responsiveness was detected to opsin in any of the three diseases. Elevated antibody titers to S-antigen were observed in some individual patients and healthy subjects. However, none of the patient groups exhibited an elevated antibody titer as compared to the control group.Although serpiginous choroiditis and APMPPE share some prominent clinical characteristics, the sensitisation in the former disease may perhaps be attributed to more severe and prolonged damage of the photoreceptor cells and blood-retina barrier.A combination of previous and present results suggests that in immunological investigations of retinitis pigmentosa patients it is more effective to use human than bovine S-antigen as test antigen because a species specific epitope seems to be involved.