MicroRNAs在晶状体中的功能

MicroRNAs(miRNAs)是一类包含21～23个碱基的非编码单链小分子RNA。通过与靶基因3'端非翻译区(UTR)不完全碱基配对,使mRNA降解或抑制靶mRNA的翻译,进而发挥基因调控作用。miRNAs广泛参与生物体内的多种生理和病理过程,通过其表达量的上调或下调,影响细胞发育和疾病的进程。近年来许多研究表明,miRNAs在眼部的多种组织,包括晶状体、视网膜和角膜中均有表达,其异常表达可能与某些眼部疾病的发生、发展有密切关系。本文综述近年来miRNAs在晶状体中的表达、功能及研究进展,以期寻求可用于临床诊断、治疗晶状体混浊的新型靶点。     

哺乳动物视网膜microRNA的表达及功能

microRNAs(miRNAs)是一类长约22个核苷酸的内源性非编码单链RNA,在维系几乎所有组织或器官系统的正常发育和生理功能等方面都起着非常重要的作用,主要通过降解靶基因mRNAs或抑制靶基因mRNAs的翻译,从而沉默特定靶基因发挥作用.据预测人类超过1/3的蛋白编码基因受miRNAs的调控.越来越多的研究表明很多miRNAs在眼部组织中有特异性的表达,其中至少有78个miRNAs在视网膜组织中表达.本文主要就miRNAs在哺乳动物视网膜中的表达及其相关功能的最新研究进展作一综述.     

miRNA在新生血管性眼病中作用的研究进展

微小RNA( miRNAs)是一类高度保守、非编码的小分子RNA,通过与靶基因转录的mRNA互补配对在转录后水平调节靶基因的表达,人类约有1/3的基因受miRNAs调控.新生血管性眼病是眼科的难治性疾病和重要的致盲原因.最新研究表明,miRNAs在眼内新生血管的发生发展中起到十分重要的调控作用.miRNAs用于治疗新生血管性眼病具有广阔的前景.就miRNAs的功能及其在眼部的表达、miRNAs与眼内新生血管及血管生成因子的关系、miRNAs在糖尿病视网膜病变中的研究现状进行综述.     

microRNAs与晶状体疾病的相关性研究进展

microRNAs是一类长度约22个核苷酸的内源性非编码小RNA分子,广泛存在于真核细胞中,在细胞增殖、凋亡、分化、肿瘤发生以及机体代谢等一系列生命过程中扮演了重要角色,是近年来基因调控研究的热点。许多microRNAs广泛表达于眼部多种组织,并具有组织特异性和时序特异性,可能与眼部组织的生长、发育、功能调节、疾病发生等方面密切相关。研究microRNAs在晶状体发育和病理生理过程中的作用为进一步阐明晶状体疾病的发生机制、探索相关疾病的诊断和治疗方法提供了一种新思路。     

骨形态发生蛋白在眼部发育和眼科疾病发生中的作用

骨形态发生蛋白属转化生长因子β超家族成员,参与众多器官的发生与形成.近年研究发现,骨形态发生蛋白及其受体不仅在眼部组织的发育过程中有表达,而且还参与眼部疾病的发生过程,如角膜疾病、视网膜疾病和青光眼等,表明骨形态发生蛋白在眼部发育和眼病发生中可能具有一定的作用.     

microRNAs调控近视发生发展的研究进展

近视是目前世界上最常见的人类眼部疾病之一。微小RNA (microRNAs,miRNAs)是一类长度约20~25个核苷酸的非蛋白编码的小分子单链RNA,能广泛参与基因转录后水平的调控,与机体的生理病理过程密切相关。近年来,miRNAs在近视发生发展中的调控作用引起了研究人员的广泛关注。本文就miRNAs在近视发生发展过程中的调控作用及可能涉及的通路进行综述,以期为近视发生发展的机制研究和分子生物学诊断提供思路。     

microRNAs在糖尿病视网膜病变中作用的研究进展

microRNAs(miRNAs)是一种具有调节基因表达功能的非编码小RNA分子,可以在包括血清或血浆在内的许多生物液中由细胞和组织释放.大量研究已经证实不同的miRNAs在糖尿病视网膜病变(DR)中的表达可特异性增高或减少,最近越来越多的证据表明血清和血浆中某些miRNAs在DR中存在特异性表达并参与DR的发生发展,...     

促红细胞生成素在眼部新生血管疾病发病中的作用

眼部新生血管是一组难治性致盲性眼病的共同临床表现.多种促新生血管因子是其发病的主要机制.促红细胞生成素(erythropoietin,EPO)不仅具有调节红细胞生成的作用,也是一种促新生血管因子,在生理和病理性血管形成过程中起重要作用.EPO在角膜新生血管、视网膜新生血管等形成过程中表达增加,在氧诱导的视网膜新生血管动物模型中,阻断EPO信号可以抑制新生血管形成.这些研究提示EPO在眼部新生血管疾病中起重要作用,有望成为治疗眼部新生血管的新靶点.     

趋化因子与眼部新生血管性疾病研究进展

趋化因子是机体内一组具有趋化作用的细胞因子,主要表达于中性粒细胞、单核细胞、巨噬细胞、T淋巴细胞和B淋巴细胞,眼部的组织细胞及免疫活性细胞亦可分泌产生多种趋化因子.研究表明,趋化因子在炎症反应、感染、创伤愈合、免疫调节、血管发生、肿瘤的侵袭和转移等生理病理过程中发挥重要作用.高糖、缺氧、氧化应激等因素刺激眼部组织细胞上调CXC趋化因子、CC趋化因子的表达,参与脉络膜新生血管(CNV)及眼部新生血管性疾病的发展.就趋化因子的基本概念和功能以及其与常见眼部新生血管性疾病,如糖尿病视网膜病变(DR)、年龄相关性黄斑变性(AMD)的关系进行综述.     

硫氧还蛋白在眼部疾病发病中的保护作用

硫氧还蛋白(TRx)是一种广泛表达于真核细胞和原核细胞的内源性蛋白质,其活性位点的邻位双巯基使其具有强大的还原活性,能有效还原蛋白质-蛋白质二硫化物,对于维持细胞内氧化还原的稳态具有重要的作用.近年来研究表明,TRx具有多种功能,对人体多种疾病的发生和发展具有保护作用,包括眼部疾病.TRx与年龄相关性白内障、脉络膜新生血管性疾病、视网膜疾病以及视神经疾病等都有密切的关系,许多研究对上述疾病过程中TRx的保护性作用机制进行研究和探讨,为探讨眼科疾病新的治疗方法提供依据.     

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.     

miRNA与白内障发病机制相关的研究进展

微小RNA(miRNA)是一种广泛存在的小的非编码RNA(ncRNA),长度为20-25个核苷酸。眼部组织中存在的miRNA通过参与细胞生长、增殖、分化和凋亡等过程在正常眼中发挥关键作用。白内障是全球致盲的主要原因,研究表明,miRNA与白内障的发生发展有关,其作为治疗和预防白内障的潜在靶点具有新的应用前景。文章通过氧化损伤、凋亡、自噬和上皮-间充质转化(EMT)等不同发病机制对miRNA在白内障发生发展过程中的研究进展进行综述。     

Altered Regulation of mRNA and miRNA Expression in Epithelial and Stromal Tissue of Keratoconus Corneas

PurposeEvaluation of mRNA and microRNA (miRNA) expression in epithelium and stroma of patients with keratoconus.MethodsThe epithelium and stroma of eight corneas of eight patients with keratoconus and eight corneas of eight non-keratoconus healthy controls were studied separately. RNA was extracted, and mRNA and miRNA analyses were performed using microarrays. Differentially expressed mRNAs and miRNAs in epithelial and stromal keratoconus samples compared to healthy controls were identified. Selected genes and miRNAs were further validated using RT-qPCR.ResultsWe discovered 170 epithelial and 1498 stromal deregulated protein-coding mRNAs in KC samples. In addition, in epithelial samples 180 miRNAs and in stromal samples 379 miRNAs were significantly deregulated more than twofold compared to controls. Pathway analysis revealed enrichment of metabolic and axon guidance pathways for epithelial cells and enrichment of metabolic, mitogen-activated protein kinase (MAPK), and focal adhesion pathways for stromal cells.ConclusionsThis study demonstrates significant differences in the expression and regulation of mRNAs and miRNAs in the epithelium and stroma of Patients with KC. Also, in addition to the well-known target candidates, we were able to identify further genes and miRNAs that may be associated with keratoconus. Signaling pathways influencing metabolic changes and cell contacts are affected in epithelial and stromal cells of patients with keratoconus.     

MicroRNA在葡萄膜炎发病过程中的调控作用研究进展

微小ＲＮＡ（ｍｉｃｒｏＲＮＡ,ｍｉＲＮＡ）是生物体内源性的、约１９～２４个核苷酸构成的非编码单链ＲＮＡ分子。ｍｉＲＮＡ可以与靶标ｍＲＮＡ基因的３’端非编码区域（３’ＵＴＲ）互补结合,从而在转录后水平负调控靶基因的表达。ｍｉＲＮＡ通过降解靶基因或者抑制转录后的翻译水平,进而影响细胞的分化、增殖和凋亡,并在生物生长发育和疾病发生发展过程中发挥重要的调节作用。近年来研究表明,ｍｉＲＮＡ在葡萄膜炎的发生发展进程中同样发挥重要的调控作用。本文就ｍｉＲＮＡ在葡萄膜炎发生发展过程中的调控作用作一综述,为深入研究葡萄膜炎的发病机理提供新思路。     

MicroRNAs在视网膜病变中作用的研究进展

微小ＲＮＡ（ｍｉｃｒｏＲＮＡｓ,ｍｉＲＮＡｓ）是近年来发现的普遍存在于生物基因组的非编码蛋白质的单链小ＲＮＡ,长约２２个核苷酸,它们通过在转录后和翻译水平调节基因表达而调控生理和病理过程。视网膜病变是眼科难治性疾病和致盲的重要原因。最新研究表明,ＭｉｃｒｏＲＮＡｓ在视网膜病变的发生发展中起到十分重要的调控作用。ＭｉｃｒｏＲＮＡｓ用于治疗视网膜病变具有广阔的前景。本文就ＭｉｃｒｏＲＮＡｓ的功能及其在视网膜病变中的研究现状进行综述。     

Levels of mRNA encoding proteins of the cGMP cascade as a function of light environment.

The levels of the retinal mRNAs encoding opsin, the alpha subunit of rod transducin (T alpha), S-antigen (S-ag) and the gamma subunit of rod-specific cGMP-phosphodiesterase (cGMP-PDE) were measured in rats reared in cyclic light or darkness and after adaptation for different periods of time to the opposite light environment. We found that rats changed from cyclic light to darkness, gradually increased their retinal content of opsin and T alpha mRNAs but decreased their levels of S-ag mRNA. The reverse results were obtained when rats were changed from darkness to cyclic light. In contrast, the levels of retinal cGMP-PDE gamma mRNA remained unchanged in animals adapted to either of the two rearing light conditions. Our results indicate that some mRNAs encoding proteins associated with the cGMP cascade are responsive to environmental lighting and may be involved in the long term light or dark adaptive processes.     

外泌体源性miRNA在眼部疾病中的研究进展

外泌体是直径为30～200nm的细胞外泌性囊泡,可由多种细胞释放至细胞外空间。研究证实,外泌体中含有蛋白质、mRNA、microRNA(miRNA)等多种功能活性物质。miRNA是一类短链非编码RNA,可在转录后水平调控基因表达,参与细胞的增殖、迁移、分化等生命活动。外泌体源性miRNA可被选择性组装入外泌体,传递至邻近或远处的细胞,并调节受体细胞的功能。研究表明,外泌体源性miRNA与多种眼科疾病病的发生、发展和转归密切相关,有潜力作为新型生物标志物以指示疾病状态。本文就外泌体源性miRNA的基本特征及其在眼部疾病中的研究进展进行系统综述。     

Exosomal miR-29b found in aqueous humour mediates calcium signaling in diabetic patients with cataract

AIM: To investigate the role of exosomal miR-29b and Ca2+ in regulating the function of human lens epithelial cells (HLECs). METHODS: Exosomes were isolated from human aqueous humour (AH) by ultracentrifugation, and visualized by nanoparticle tracking and transmission electron microscopy. Exosomal miRNA sequencing was performed to identify differentially expressed miRNAs between diabetes with cataracts (DMC) group and age-related cataracts (ARC) group. TargetScan was used to predict potential target of certain miRNA. The expression of CACNA1C mRNA was determined by quantitative real-time polymerase chain reaction and CACNA1C protein was determined by Western blotting. Concentration of Ca2+ in human AH and the culture supernatant of cells were detected by the calcium assay kit. Cell counting kit-8 was used to determine cell viability. RESULTS: Exosomes were isolated from human AH, which had a typical cup-shaped phenotype and a particle size distribution in accordance with micro extracellular vesicles. Exosomal miRNA sequencing revealed that miR-29b was significantly downregulated in DMC group compared with ARC. Ca2+ concentration of human AH in DMC was higher than that in ARC. The culture supernatant of cells transfected with miR-29b inhibitors had a higher concentration of Ca2+ than that transfected with miR-29b mimics. miR-29b reduced the viability of HLECs by upregulating CACNA1C expression. CONCLUSION: Exosomes isolated from human AH contains abundant miRNAs. A significantly expressed miRNA, miR-29b, can affect the concentration of Ca2+ and regulate HLEC processes by upregulating CACNA1C.     

Altered microRNA expression profiles in retinas with diabetic retinopathy

Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to ascertain miRNAs associated with DR. Histopathologically, we observed characteristic features of DR in rats at 10 weeks after STZ injection. Investigation of miRNA expression profiles in the retinas of control and diabetic rats using miRNA microarrays revealed that many miRNAs were abnormally expressed in DR. On the basis of their fold changes and probability values, a total of 37 miRNAs were selected for further validation by real-time PCR analysis. The results showed that 11 miRNAs were significantly upregulated and 6 miRNAs were notably downregulated in DR. Furthermore, these changes in retinal miRNA expression levels paralleled the course of DR. Levels of miR-182, miR-96, miR-183, miR-211, miR-204, and miR-124 were significantly increased during the progress of DR, whereas miR-10b, miR-10a, miR-219-2-3p, miR-144, miR-338, and miR-199a-3p were significantly decreased. Our data indicate that the aberrant miRNA expression profiles in DR are associated with the development of DR. Modulation of retinal miRNA expression levels may provide a potential therapeutic strategy for DRs.