环状RNA与疾病关系的研究进展

环状RNA是最近发现的一类内源性非编码RNA,由内含子配对驱动的环化等模型产生,受相关调控因子调控。环状RNA的一个重要生物学功能是作为miRNA海绵,使miRNA水平在短时间内发生明显改变。环状RNA与疾病密切联系,是具有诊断和治疗潜力的分子。本文论述环状RNA的生物合成及调控、环状RNA的生物学功能以及环状RNA与疾病的关系。     

lncRNA与miRNA相互作用对疾病的影响

长链非编码RNA(lncRNA)与微小RNA(miRNA)之间存在相互调控关系。lncRNA可作为一种竞争性内源性RNA(ceRNA)与miRNA相互作用,参与靶基因的表达调控,反之,miRNA可通过RNA诱导沉默复合物(RISC)调控lncRNA发挥生物学功能,两者共同参与多种疾病的发生。     

miRNA与固有免疫

miRNA是近年来发现的一种小分子RNA,参与细胞分化、生长发育等多种生物学过程,与人类疾病密切相关。最近,有研究发现miRNA可以通过TLR的信号转导途径和细胞因子反应参与固有免疫。本文对miRNA和RNA干扰在固有免疫反应中的调控作用作一综述。     

miRNA在心脏发育和心血管疾病中的研究进展

miRNA是内源性非编码微小RNA,长度约22个核苷酸.愈是高等生物,miRNA数量愈多,这可能是高等生物生命多样化的原因之一.而且,在不同物种之间,其序列高度保守.miRNA通过调控靶基因表达参与调控多种生物学过程,并且与疾病发生发展密切相关.近来的研究证实,miRNA广泛参与心脏发育和心血管疾病发生发展.本综述将总结miRNA在心血管发育中的作用以及在心脏疾病中的作用机制,探讨目前的miRNA的研究策略,以及miRNA作为诊断标记物和药物治疗靶点的可能性.     

microRNA 在自身免疫性疾病中的研究进展

<正>microRNA(miRNA)是一类能够调节基因表达的短单链内源非编码RNA,人体30%编码蛋白的RNA受miRNA调节,这种带有茎-环结构的miRNA主要通过与互补的mRNA结合引起RNA降解或翻译抑制,对基因的表达起调控作用[1],进而调节细胞发育、增殖、分化、凋亡以及肿瘤的发生。近来研究发现miRNA在多种自身免疫性疾病中存在异常表达,提示miRNA与多种自身免疫性疾病的发生、     

微RNA在中枢神经系统疾病中的研究进展

微RNA(miRNA)是一类重要的调节转录后基因表达水平的内源性非编码RNA,参与细胞生长和组织分化等多种生理病理过程。近年来,对miRNA在中枢神经系统疾病中的研究逐渐增多且多聚焦于某几个miRNA。因此,本文综述了目前在中枢神经系统疾病中研究的热点miRNA,阐述了这些miRNA在阿尔茨海默病(AD)、帕金森病(PD)、抑郁症和药物成瘾中的表达变化及作用机制,以期为中枢神经系统疾病机制的研究和诊断治疗提供新方向。     

小RNA的研究现状

长期以来,人们认为RNA只是起到遗传信息“桥梁”的作用,从DNA获得遗传信息再转化成蛋白质。然而,近十几年的研究表明——小RNA在基因调控和生长发育等方面发挥着重要作用。小RNA主要包括两大类：siRNA和miRNA。它们的功能既有相似又有差异,siRNA主要参与RNA干涉,而miRNA形成核糖核蛋白复合体(miRNP)调控基因表达。本文从siRNA和miRNA的结构、功能以及与人类疾病关系等方面综述了小RNA的最新研究进展。     

microRNA的组织特异性表达及其检测方法

microRNA（miRNA）是一类调节基因表达的非编码的小RNA。miRNA参与细胞的分化、增殖及凋亡等多种生命活动,并与多种疾病的发生和发展密切相关。miRNA表达存在组织特异性,而疾病（包括肿瘤）的发生和发展也表现为某些miRNA的表达失调。miRNA相关研究均需检测细胞的miRNA表达水平,常用杂交和RT—PCR等方法检测。     

与心脏发育相关的miRNA研究

microRNA(miRNA)是生物体内源长度约为20～23个核苷酸的非编码小RNA,在生物体发育、细胞增殖与分化等过程中扮演了重要角色.心脏是人体的重要器官之一,miRNA与心脏发育密切相关,很多分子生物学研究技术已经应用到对心脏发育的研究中,研究表明一些特异miRNA有可能为心脏疾病的诊断和治疗提供新的靶点和研发新的药物.     

microRNA在淋巴细胞分化及淋巴瘤发生中作用的研究进展

microRNA(miRNA)是一类长度约21～23个核苷酸的小RNA,不编码蛋白质,但能在转录后或者翻译水平上影响基因表达.最近的研究发现,miRNA的主要功能是调节生物体内在与机体生长、发育、疾病发生过程有关基因的表达.越来越多的证据表明,miRNA在造血细胞分化发育、免疫细胞功能和肿瘤发生方面发挥着重要的作用,本文就miRNA在T细胞和B细胞分化中的作用及其与淋巴瘤关系的研究进展做一综述.     

Innate immunity dysregulation in aging eye and therapeutic interventions

The prevalence of eye diseases increases considerably with age, resulting in significant vision impairment. Although the pathobiology of age-related eye diseases has been studied extensively, the contribution of immune-related changes due to aging remains elusive. In the eye, tissue-resident cells and infiltrating immune cells regulate innate responses during injury or infection. But due to aging, these cells lose their protective functions and acquire pathological phenotypes. Thus, dysregulated ocular innate immunity in the elderly increases the susceptibility and severity of eye diseases. Herein, we emphasize the impact of aging on the ocular innate immune system in the pathogenesis of infectious and non-infectious eye diseases. We discuss the role of age-related alterations in cellular metabolism, epigenetics, and cellular senescence as mechanisms underlying altered innate immune functions. Finally, we describe approaches to restore protective innate immune functions in the aging eye. Overall, the review summarizes our current understanding of innate immune functions in eye diseases and their dysregulation during aging.     

Leflunomide: Inhibition of S-antigen induced autoimmune uveitis in Lewis rats

Leflunomide (LEF) is a novel immunomodulator which has been reported to be efficacious in experimental models of systemic autoimmune diseases and in treating rheumatoid arthritis in man. Leflunomide's ability to ameliorate ocular disease processes was investigated in a model of autoimmune eye disease, experimental autoimmune uveitis (EAU). EAU was induced by the injection of retinal S-antigen (S–Ag) into the foot-pad of Lewis rats. Leflunomide, or the reference compound cyclosporin A (CSA), was administered orally or topically (to one eye) each day beginning on the day of S–Ag injection. Drug efficacy was measured by the suppression in clinical signs of ocular inflammation and confirmed by histology. Both oral and topical ocular treatment with LEF suppressed the ocular disease signs and symptoms and retinal necrosis and reduced the S–Ag antibody levels associated with EAU in a dose-dependent manner. Both LEF and CSA were able to inhibit totally the disease manifestations of EAU; however, a comparison of the IC₅₀ and IC₉₀ values indicate that LEF is more potent than CSA in inhibiting EAU. These results suggest that leflunomide may be useful for treating autoimmune diseases of the eye.     

Orbital position and eye movement influences on visual responses in the pulvinar nuclei of the behaving macaque

Summary We studied the influences of eye movements on the visual responses of neurons in two retinotopically organized areas of the pulvinar of the macaque. Cells were recorded from awake, trained monkeys, and visual responses were characterized immediately before and after the animals made saccadic eye movements. A significant proportion of the cells were more responsive to stimuli around the time of eye movements than they were at other intervals. Other cells had response reduction. For some neurons, the change in excitability was associated with orbital position and not the eye movement. For other cells the change was present with eye movements of similar amplitude and direction but with different starting and ending positions. Here it appears that the eye movement is the important parameter. Other cells had effects related to both eye position and eye movements. In all cells tested, the changes in excitability were present when the experiments were conducted in the dark as well as in the light. This suggests that the mechanism of the effect is related to the eye position or eye movement and not visual-visual interactions. For about half of the neurons with modulations, the response showed facilitation for stimuli presented in the most responsive region of the receptive field but not for those at the edge of the field. For the other cells there was facilitation throughout the field. Thus, a gradient of modulation in the receptive field may vary among cells. These experiments demonstrate modulations of visual responses in the pulvinar by eye movements. Such effects may be part of the visual-behavioral improvements at the end of eye movements and/or contribute to spatial constancy.     

An eye movement recording method operating with a closed eye

An eye movement recorder, based on an optoelectronic method, can be used in closed or open eye situations. Three photodiodes are used as proximity sensors. This eye tracker is well adapted for the studies of eye movement in after-image phenomena.     

A comparison of head-unrestrained and head-restrained pursuit: influence of eye position and target velocity on latency

Horizontal step-ramp target trajectories were used to study the initiation of head-unrestrained and head-restrained pursuit in the monkey. In a first series of experiments, initial target position (0 degrees, 5 degrees, or 30 degrees, contraversive to the direction of pursuit), fixation duration, target velocity (20 degrees, 40 degrees, 60 degrees and 80 degrees/s), and target direction were randomized in order to minimize predictive responses. Animals pursued the target either with their eyes alone (head-restrained: HR condition) or with a combination of eye and head movements (head-unrestrained: HU condition). Head motion onset consistently lagged pursuit onset (i.e., eye motion) by 50 ms or more in the HU condition, and was influenced by target velocity as well as by initial target position. Pursuit onset latencies did not vary systematically as a function of target velocity in either the HR or HU conditions. However, pursuit initiation latencies tended to be longer in the HU condition as compared to the HR condition when target motion started from the most contraversive position. A second series of experiments revealed that this difference in HR and HU pursuit onset latencies could be explained by the effects of initial eye-in-head position; more contraversive initial eye positions yielded shorter pursuit latencies in both conditions, and the monkeys generally moved their head towards the target in the HU condition, resulting in smaller eye-in-head eccentricities. Furthermore, we found that initial gaze and head positions had little or no effect on pursuit latencies. We conclude that the latency for pursuit initiation is similar irrespective of whether an animal is head-restrained or head-unrestrained, when initial eye position is held constant.     

eyeVarP: A computational framework for the identification of pathogenic variants specific to eye disease

PurposeDisease-specific pathogenic variant prediction tools that differentiate pathogenic variants from benign have been improved through disease specificity recently. However, they have not been evaluated on disease-specific pathogenic variants compared with other diseases, which would help to prioritize disease-specific variants from several genes or novel genes. Thus, we hypothesize that features of pathogenic variants alone would provide a better model.MethodsWe developed an eye disease–specific variant prioritization tool (eyeVarP), which applied the random forest algorithm to the data set of pathogenic variants of eye diseases and other diseases. We also developed the VarP tool and generalized pipeline to filter missense and insertion-deletion variants and predict their pathogenicity from exome or genome sequencing data, thus we provide a complete computational procedure.ResultseyeVarP outperformed pan disease–specific tools in identifying eye disease–specific pathogenic variants under the top 10. VarP outperformed 12 pathogenicity prediction tools with an accuracy of 95% in correctly identifying the pathogenicity of missense and insertion-deletion variants. The complete pipeline would help to develop disease-specific tools for other genetic disorders.ConclusioneyeVarP performs better in identifying eye disease–specific pathogenic variants using pathogenic variant features and gene features. Implementing such complete computational procedure would significantly improve the clinical variant interpretation for specific diseases.     

Museum application of an eye tracker

The paper presents an eye tracking system specifically designed for the recording of eye movements from the visitors of a museum. Eye movements are calculated from the images of a near infra-red camera viewing the eye during the presentation of a sequence of slides. Thereafter, the same slides are displayed with the scanning paths superimposed. Servo systems, ‘intelligent’ image processing algorithms and interactive procedures have been implemented so that the eye tracker can operate on the general public without any technical supervision.     

Vertical and torsional optokinetic eye movements in the rabbit

Summary Rabbits were placed inside a striped drum, which was rotated at selected constant speeds around the animal's sagittal or bitemporal axis. Eye position was recorded by means of the scleral search coil system. A regular vertical or rotatory optokinetic nystagmus (OKN) was constantly obtained. The ratioslow phase eye velocity/drum velocity (=gain) amounted to 0.7–0.9 for stimulus velocities up to 1°/sec, and declined progressively for higher stimulus velocities. The overall input-output relations for torsional and vertical OKN were very similar to those found previously for horizontal OKN. Upward and downward motion were equally effective as a stimulus for each eye apart. The same was true for nasal and temporal rotation.In darkness, rotatory and vertical drift of the eye was seen, as described before for the horizontal plane. These findings support the hypothesis that the OKN system stabilizes the eyes on the (non-rotating) visual surroundings.It is proposed that vertical, torsional as well as horizontal OKN are mediated by sub-sets of similar retinal direction-selective cells as described in the literature.     

Shared and distinct oculomotor function deficits in schizophrenia and obsessive compulsive disorder

Detailed analysis of oculomotor function phenotypes in antisaccade, smooth eye pursuit, and active fixation tasks was performed in a sample of 44 patients with schizophrenia, 34 patients with obsessive compulsive disorder (OCD), and 45 matched healthy controls. A common pattern of performance deficits in both schizophrenia and OCD emerged including higher antisaccade error rate, increased latency for corrective antisaccades, as well as higher rates of unwanted saccades in smooth eye pursuit compared to healthy controls. This common pattern could be related to the dysfunction of a network of cognitive control that is present in both disorders, including the dorsolateral prefrontal cortex, the posterior parietal cortex, and the anterior cingulate cortex. In contrast, only patients with schizophrenia showed a specific increase for correct antisaccade mean latency and the intrasubject variability of latency for error prosaccades as well as a decrease in the gain for smooth eye pursuit, suggesting a specific deficit in saccadic motor control and the frontal eye field in schizophrenia that is not present in OCD. A specific deficit in fixation stability (increased frequency of unwanted saccades during active fixation) was observed only for OCD patients pointing to a deficit in the frontostriatal network controlling fixation. This deficit was pronounced for OCD patients receiving additional antipsychotic medication. In conclusion, oculomotor function showed shared and distinct patterns of deviance for schizophrenia and OCD pointing toward shared and specific neurobiological substrates for these psychiatric disorders.     

The role of complement system in ocular diseases including uveitis and macular degeneration

In the normal eye, the complement system is continuously activated at low levels and both membrane-bound and soluble intraocular complement regulatory proteins tightly regulate this spontaneous complement activation. This allows protection against pathogens without causing any damage to self-tissue and vision loss. The complement system and complement regulatory proteins control the intraocular inflammation in autoimmune uveitis and play an important role in the development of corneal inflammation, age-related macular degeneration and diabetic retinopathy. The evidence derived from both animal models and patient studies support the concept that complement inhibition is a relevant therapeutic target in the treatment of various ocular diseases. Currently, several clinical trials using complement inhibitors are going on. It is possible that, in the near future, complement inhibitors might be used as therapeutic agents in eye clinics.