BMP4/Smad信号通路的分子机制及其在眼部疾病中的作用

骨形成蛋白4（BMP4）通过Smad信号通路向下游传递信号,同时与Wnt/β-catenin、FGF等信号通路相互作用,调节一系列的病理生理活动。BMP4/Smad信号通路对眼具有重要作用。BMP4/Smad信号通路与眼前节、晶状体、视网膜的发育密切相关。同时,BMP4在成熟眼组织中高度表达,意味着BMP4/Smad信号通路与某些眼部疾病的发病机制有关。BMP4/Smad信号通路在维持角膜上皮稳态、视网膜神经的保护及修复方面起一定作用,同时还与青光眼、年龄相关性黄斑变性、增生型玻璃体视网膜病变等疾病的发生密切相关。本文主要讲述了BMP4/Smad信号通路的分子机制,并详细介绍了BMP4/Smad信号通路在眼发育和一些眼部疾病中的作用。     

Hedgehog信号通路在视网膜细胞发育及病理性血管生成中的作用

视网膜细胞发育障碍和眼部血管的病理性生长可见于多种眼部疾病,严重影响患者视力.Hedgehog信号转导通路已被证实参与视网膜神经节细胞、无长突细胞、视锥细胞、视杆细胞、Müller胶质细胞、视网膜色素上皮(RPE)细胞等细胞生长发育的多个过程.近年来研究表明,Hedgehog信号通路可以调控视网膜细胞的分化和发育,并在眼部新生血管生成中起到关键性作用.本文从Hedgehog信号通路的组成、Hedgehog信号通路与视网膜细胞发育、视网膜再生、Hedgehog信号通路与眼部病理性血管生成4个方面就Hedgehog信号通路在视网膜细胞发育及病理性血管生成中的作用进行综述,以期为视网膜及眼部血管性疾病的治疗提供新的靶点.     

Notch信号通路在视网膜细胞发育及血管生成中的作用

视网膜细胞变性和新生血管形成存在于多种常见眼病的发生和发展过程中,严重损害患者视力,甚至致盲.多项研究结果表明Noah信号通路参与调控多种器官和组织的发育及细胞分化过程,因此,有必要就Notch信号通路的组成及其在视网膜细胞发育和血管发生过程中的作用进行综述,以期为视网膜疾病的防治研究提供新的思路和作用靶点.     

TGFβ/Smads信号传导通路与眼部疾病

转化生长因子β是目前公认的与创伤愈合和纤维化关系最为密切的生长因子,Smad蛋白家族是TGFβ细胞内信号传导的重要因子.TGFβ/Smads信号传导系统在角膜的形成发育、角膜和晶状体创伤后的修复、后发性白内障、原发性开角型青光眼、增生性视网膜病变以及青光眼滤过性手术后瘢痕化形成中均起着至关重要的作用.通过调节Smad蛋白可以影响眼部组织的创伤愈合和纤维化程度.本文就TGFβ/Smads信号传导通路与相关眼部疾病作一综述.     

增生性玻璃体视网膜病变发生机制主要信号通路研究进展

增生性玻璃体视网膜病变(PVR)是发生在视网膜上的无血管纤维增生性疾病, 主要病理改变为视网膜色素上皮细胞(RPE)及胶质细胞在玻璃体和视网膜上增殖和牵拉。基础研究证实PVR的形成和多条信号通路有关, 主要包括NF-κB信号通路, MAPK及其下游信号通路, JAK/STAT信号通路, PI3K/Akt信号通路, 凝血酶及其受体通路, TGF-β及下游信号通路, North信号通路及Wnt/β-连环蛋白信号通路等。本文总结了PVR形成机制中的主要信号通路的研究进展, 为PVR药物治疗研究提供依据和支持。     

血管生成素在眼部发育和相关眼病中的作用

血管生成素和相应的酪氨酸激酶受体构成了Ang-Tie信号通路,对于眼部脉管系统的生理性发育以及病理条件下的相关眼部疾病均发挥重要作用。在眼球发育期,Ang-Tie信号通路参与视网膜血管发育、原始玻璃体血管消退以及房角房水引流通道发育等。在成熟个体中,Ang-Tie信号通路在维持血管稳定方面发挥重要作用,其失衡可破坏内皮...     

视网膜钾离子及其通道与近视相关研究进展

视网膜视觉信号处理与近视的发生发展关系密切,其中视网膜离子通道活动在近视相关信号通路中扮演着一定角色。近年来发现,视网膜钾离子的转运参与了眼部屈光发育和近视的形成。本文从视网膜钾离子转运与屈光发育和参与近视形成的可能机制、视觉相关视网膜钾离子通道,以及近视相关钾离子通道基因等方面对这一领域的相关研究进行综述。     

Hippo通路及其在眼科领域的研究进展

Hippo通路是一个进化上保守的信号通路,它受细胞内外多种因素的调控,通过效应分子YAP/TAZ,参与调节细胞的增殖、分化、迁移和再生等多种重要生理活动,其在组织发育、器官再生以及肿瘤发生等方面均有广泛的研究。近年来的研究显示,Hippo通路与眼部组织的发育、再生和眼部疾病联系密切。阐明Hippo通路在眼部组织中的作用有助于揭示眼科疾病发生发展的机制,对完善眼科基础研究,指导眼科临床工作都具有深远的意义。本文从Hippo通路的核心组分、生物学作用以及近年来Hippo通路在眼部组织如角膜、小梁网、晶状体、视网膜和葡萄膜中的研究进展进行了详细综述。     

Hippo/YAP信号通路在眼部作用的研究进展

Hippo-YAP通路在机体发育和疾病发生中均具有重要作用。Hippo-YAP通路的调节紊乱可能导致病理组织过度生长和肿瘤的进展；近年来研究发现，Hippo-YAP信号通路的异常调节可能与眼部疾病相关，如圆锥角膜、Sveinsson 脉络膜视网膜萎缩和视网膜变性等，本文就Hippo/YAP 在眼部作用的研究进展进行系统综述，为眼部疾病的治疗提供理论基础。     

Wnt及BMP信号通路在眼球发育中的作用

脊椎动物的眼球发育是受多种信号分子及其构成的通路网络参与调控的复杂生物学过程。近年来，Wnt信号通路和BMP信号通路在眼球发育过程中的作用日益受到关注，并且发现两条信号通路之间存在着相互作用，在调控眼球发育过程中伴有彼此通路中的关键分子的表达水平和功能活性的改变，在一定条件下表现出对眼球发育特异性标志物调控的协同或拮抗效应。本文就Wnt及BMP两条重要的信号通路在调控眼球发育方面的进展进行综述。     

The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease

The Wnt signaling pathway is highly conserved among species and has an important role in many cell biological processes throughout the body. This signaling cascade is involved in regulating ocular growth and development, and recent findings indicate that this is particularly true in the retina. Mutations involving different aspects of the Wnt signaling pathway are being linked to several diseases of retinal development. The aim of this article is to first review the Wnt signaling pathway. We will then describe two conditions, familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND), which have been shown to be caused in part by defects in the Wnt signaling cascade.     

The Wnt Signaling Pathway in Familial Exudative Vitreoretinopathy and Norrie Disease

The Wnt signaling pathway is highly conserved among species and has an important role in many cell biological processes throughout the body. This signaling cascade is involved in regulating ocular growth and development, and recent findings indicate that this is particularly true in the retina. Mutations involving different aspects of the Wnt signaling pathway are being linked to several diseases of retinal development.

The aim of this article is to first review the Wnt signaling pathway. We will then describe two conditions, familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND), which have been shown to be caused in part by defects in the Wnt signaling cascade.     

PI3K/Akt信号通路在眼科疾病发生发展过程中的调控作用研究进展

眼科疾病的发生发展与眼组织的异常发育和功能障碍有关,其中相关信号通路的活化在眼科疾病的发生和发展过程中发挥重要作用.PI3 K/Akt信号通路(磷脂酰肌醇3激酶/蛋白激酶B信号通路)广泛存在于各类细胞中,是参与细胞生长、增殖、分化调节的重要信号转导通路.研究发现,PI3 K/Akt信号通路在白内障、糖尿病视网膜病变等多...     

Rho/ROCK信号通路参与年龄相关性黄斑变性调控机制的研究现状

年龄相关性黄斑变性（AMD）已被认为是最严重的眼科疾病之一。遗传、老化、氧化应激和炎症等在AMD发生发展中起着重要作用,而且Rho激酶在很多细胞周期过程中发挥着重要作用,Rho/ROCK通路的异常激活参与了AMD的发病过程。本文对Rho/ROCK信号通路的结构、活化、功能、调控AMD的病理机制以及靶向Rho/ROCK通路治疗AMD的潜力进行综述。     

TGF-BETA信号通路介导的眼组织纤维化在眼病发生发展中作用的研究进展

眼科疾病的发生发展与眼组织的异常发育和功能障碍有关,其中相关信号通路的异常活化可使眼组织纤维化进而使其生理功能发生障碍,在眼病的发生和发展过程中发挥重要作用。转化生长因子β(TGF-β)信号通路广泛存在于各类细胞中,可参与细胞的生长、增殖和分化调节,是介导组织发生纤维化的关键信号通路。有研究发现,TGF-β信号通路可在青光眼、眼眶纤维化、增生性玻璃体视网膜病变等眼病中发挥作用。本文就TGF-β信号通路介导的眼组织纤维化在眼病发生发展中的作用研究进展进行简要综述。     

TGFβ promotes Wnt expression during cataract development

TGFβ induces lens epithelial cells to undergo epithelial mesenchymal transition (EMT) and many changes with characteristics of fibrosis including posterior capsular opacification (PCO). Consequently much effort is directed at trying to block the damaging effects of TGFβ in the lens. To do this effectively it is important to know the key signaling pathways regulated by TGFβ that lead to EMT and PCO. Given that Wnt signaling is involved in TGFβ-induced EMT in other systems, this study set out to determine if Wnt signaling has a role in regulating this process in the lens. Using RT-PCR, in situ hybridization and immunolocalization this study clearly shows that Wnts 5a, 5b, 7b, 8a, 8b and their Frizzled receptors are upregulated in association with TGFβ-induced EMT and cataract development. Both rat in vitro and mouse in vivo cataract models show similar profiles for the Wnt and Frizzled mRNAs and proteins that were assessed. Currently it is not clear if the canonical β-catenin/TCF signaling pathway, or a non-canonical pathway, is activated in this context. Overall, the results from the current study indicate that Wnt signaling is involved in TGFβ-induced EMT and development of fibrotic plaques in the lens.     

TGFbeta promotes Wnt expression during cataract development

TGFbeta induces lens epithelial cells to undergo epithelial mesenchymal transition (EMT) and many changes with characteristics of fibrosis including posterior capsular opacification (PCO). Consequently much effort is directed at trying to block the damaging effects of TGFbeta in the lens. To do this effectively it is important to know the key signaling pathways regulated by TGFbeta that lead to EMT and PCO. Given that Wnt signaling is involved in TGFbeta-induced EMT in other systems, this study set out to determine if Wnt signaling has a role in regulating this process in the lens. Using RT-PCR, in situ hybridization and immunolocalization this study clearly shows that Wnts 5a, 5b, 7b, 8a, 8b and their Frizzled receptors are upregulated in association with TGFbeta-induced EMT and cataract development. Both rat in vitro and mouse in vivo cataract models show similar profiles for the Wnt and Frizzled mRNAs and proteins that were assessed. Currently it is not clear if the canonical beta-catenin/TCF signaling pathway, or a non-canonical pathway, is activated in this context. Overall, the results from the current study indicate that Wnt signaling is involved in TGFbeta-induced EMT and development of fibrotic plaques in the lens.