巨噬细胞极化在眼科疾病发生发展过程中的作用机制研究进展

巨噬细胞是单核吞噬细胞系统的主要细胞群,充当先天性免疫和适应性免疫的哨兵.在微环境信号作用下,巨噬细胞可被不同的激活物极化为不同功能的M1型、M2型巨噬细胞.巨噬细胞极化既可以发生在生理条件下,也可以发生在病理条件下,并贯穿疾病发生、发展以及转归的全过程.很多眼科疾病的病理过程都和巨噬细胞极化密切相关,巨噬细胞极化及炎...     

M2型巨噬细胞极化在胸腺基质淋巴细胞生成素及其下游分子诱导过敏性结膜炎发病机制中作用的研究进展

过敏性结膜炎(AC)是人类眼表一种常见的过敏性疾病,发病原因复杂,主要是由免疫球蛋白E或T淋巴细胞介导的一种免疫反应。目前,过敏效应阶段细胞因子之间相互作用的分子机制已明确,但对过敏上游因子的了解却知之甚少。有研究结果表明,作为过敏上游因子的胸腺基质淋巴细胞生成素(TSLP)等具有启动和促过敏作用;此外,在短豚草花粉诱导实验性AC小鼠模型中已证实M2型巨噬细胞极化在辅助性T淋巴细胞2(Th2)显性过敏性炎症中有重要作用。目前,TSLP和M2型巨噬细胞在AC发病过程中的作用机制尚未完全阐明。因此,本文中笔者就M2型巨噬细胞极化在TSLP及其下游分子诱导AC发病机制中的作用进行综述。     

巨噬细胞的异质性在视网膜新生血管中的作用

视网膜血管疾病是临床上一类病因复杂、机制尚不明确的致盲眼病，其主要的病理生理学特征是视网膜新生血管形成。大量的基础研究和临床证据证实，免疫相关巨噬细胞（macrophages，MФ）在视网膜新生血管形成中发挥着重要作用。MФ可分为经典活化的、促炎性的M1型和替代活化的、免疫抑制性的M2型，M2型MФ根据刺激信号和功能的不同又可分为M2a、M2b、M2c 3种。而MФ的不同亚型在视网膜新生血管形成发生发展中的作用还存在争议。因此，明确其不同亚型的具体作用，对深入理解视网膜新生血管形成性疾病的发病机制和临床治疗十分关键。（国际眼科纵览， 2018,  42:  119-124）     

巨噬细胞活化在眼底疾病发病中的作用

巨噬细胞是一种位于组织内的白细胞,源自单核细胞.巨噬细胞除具有强大的吞噬功能外,还具有趋化性定向运动功能以及分泌大量细胞因子的作用.其在炎症反应、免疫调节、组织修复、局部组织微环境调控等过程中均发挥着重要作用.大量的实验研究表明,眼底疾病的发生发展与上述过程密切相关.本文就巨噬细胞活化在眼底疾病发生发展过程中的作用作一综述.     

巨噬细胞在葡萄膜炎免疫调节治疗机制中的研究进展

葡萄膜炎是一类常见的累及葡萄膜、视网膜、视网膜血管及玻璃体的顽固性致盲性的炎性疾病,它的发生与其各细胞亚群免疫机制失衡相关,巨噬细胞在机体先天免疫系统中起核心作用,能将人体内炎性致病菌有效清除,在应激反应中,巨噬细胞可通过极化参与机体的病原体反应和炎症调节,因此,为了系统地了解巨噬细胞极化平衡在葡萄膜炎的免疫调节机制中发挥的重要作用,文章主要通过对巨噬细胞的来源认识、机制通路的研究从而将其与葡萄膜炎疾病发生发展相联系,最后针对相关诊疗进展进行综述。     

泪膜与眼表微环境的研究进展

泪膜覆盖眼表,是眼表微环境的重要组成部分,其稳态失衡可以造成眼表其他细胞和组织结构与功能异常,从而加重眼表疾病的发生和发展。笔者旨在对泪膜与眼表微环境中其他的成分包括眼表上皮、角膜基质、角膜神经和眼表微生物群的作用方面进行综述,以期为眼表疾病的发病机制研究及诊疗提供新的思路。     

巨噬细胞与小胶质细胞在老年性黄斑变性发病机制中的调控作用

巨噬细胞和小胶质细胞作为视网膜主要的2种免疫系统的重要细胞,对老年性黄斑变性(AMD)的发病具有多重综合调控作用.然而在AMD不同阶段、不同亚型中,2种细胞可以是促炎症或促血管生成、致免疫或免疫耐受、组织损害或组织保护.2种细胞在AMD发病机制中的具体作用机制通路、功能状态与AMD的关系等仍需进一步阐述.巨噬细胞的定向诱导和对其功能的精确调控,是今后该研究领域的热点问题,随着研究的不断深入,有可能成为日后治疗AMD,尤其是渗出型AMD的一种有效的新方法.     

单核-巨噬细胞在早产儿视网膜病变发生中的作用

早产儿视网膜病变(retinopathy of prematurity,ROP)是一种常见而复杂的视网膜新生血管性疾病,致病因素复杂,发病机制尚未阐明,治疗棘手.近年来临床和基础研究证实,感染和炎症在其发生发展中起着重要作用.单核-巨噬细胞系统(MC/MΦ)是炎症反应的中心环节,在ROP发生中具有重要作用.     

Toll样受体信号通路和糖尿病视网膜病变的关系

糖尿病视网膜病变(diabetic retinopathy,DR)是导致失明的主要疾病之一,其发病机制尚未完全阐明.Toll样受体(Toll-like recetors,TLRs)是机体免疫系统识别、感知细菌、病毒等病原体入侵的重要分子,在机体免疫防御功能中发挥着重要作用.众多的研究提示糖尿病发病与免疫系统的激活密切相关,TLRs的激活在DR的发生发展中起着重要的作用.现就Toll样受体信号通路与糖尿病视网膜病变的关系作一综述,为DR的防治提供新的治疗手段和思路.     

Toll样受体与眼部炎性疾病

Toll样受体是一类存在于哺乳动物细胞的跨膜受体,它可以识别病原微生物保守的病原相关分子模式,参与细胞信号传导及免疫反应,在抗感染中发挥重要作用.本文就Toll样受体家族成员的结构特点、其识别病原微生物参与信号传导及宿主免疫的功能及其与眼部疾病的联系进行综述,为深入研究眼部感染性及免疫性疾病的发病机制提供帮助,为这些疾病的治疗提供新的思路和手段.     

Diverse roles of macrophages in intraocular neovascular diseases: a review

Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.     

Decreased Expression of TGR5 in Vogt-Koyanagi-Harada (VKH) Disease

ABSTRACT

Purpose: To investigate the role of G-protein-coupled bile acid receptor-1, Gpbar1 (TGR5) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

Methods: The mRNA level of TGR5, iNOS, Arg1, CD16, and CD206 in macrophages was assayed by real-time PCR. ELISA was used to detect the production of cytokines in cell culture supernatants. The frequencies of CD4⁺IFN-γ⁺ and CD4⁺ IL-17⁺ T cells were tested by flow cytometry.

Results: A decreased expression of TGR5 in M1 macrophages was observed in active VKH patients as compared with normal controls. TGR5 stimulation of M1 macrophages with INT-777 caused a shift of the inflammatory M1 toward the anti-inflammatory M2 macrophage subtype. TGR5 activation of macrophages co-cultured with CD4⁺ T cells inhibited Th1 and Th17 polarization, as well as the release of IFN-γ and IL-17 in the culture supernatant.

Conclusion: Our results show that a decreased TGR5 expression might contribute to the pathogenesis of VKH disease.     

Vitreous M2 Macrophage-Derived Microparticles Promote RPE Cell Proliferation and Migration in Traumatic Proliferative Vitreoretinopathy

PurposeTo characterize vitreous microparticles (MPs) in patients with traumatic proliferative vitreoretinopathy (PVR) and investigate their role in PVR pathogenesis.MethodsVitreous MPs were characterized in patients with traumatic PVR, patients with rhegmatogenous retinal detachment (RRD) complicated with PVR, and control subjects by flow cytometry. The presence of M2 macrophages in epiretinal membranes was measured by immunostaining. Vitreous cytokines were quantified by ELISA assay. For in vitro studies, MPs isolated from THP-1 cell differentiated M1 and M2 macrophages, termed M1-MPs and M2-MPs, were used. The effects and mechanisms of M1-MPs and M2-MPs on RPE cell proliferation, migration, and epithelial to mesenchymal transition were analyzed.ResultsVitreous MPs derived from photoreceptors, microglia, and macrophages were significantly increased in patients with traumatic PVR in comparison with control and patients with RRD (PVR), whereas no significance was identified between the two control groups. M2 macrophages were present in epiretinal membranes, and their signature cytokines were markedly elevated in the vitreous of patients with traumatic PVR. Moreover, MPs from M2 macrophages were increased in the vitreous of patients with traumatic PVR. In vitro analyses showed that M2-MPs promoted the proliferation and migration of RPE cells via activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. However, M2-MPs did not induce the expression of fibrotic proteins, including fibronectin, α-smooth muscle actin, and N-cadherin in RPE cells.ConclusionsThis study demonstrated increased MP shedding in the vitreous of patients with traumatic PVR; specifically, MPs derived from M2 polarized macrophages may contribute to PVR progression by stimulating RPE cell proliferation and migration.     

Macrophages in proliferative vitreoretinopathy and proliferative diabetic retinopathy: differentiation of subpopulations.

Macrophages have long been known to play a major role in the pathogenesis of proliferative vitreoretinal disorders. Using the monoclonal antibodies EBM11 (pan macrophage), 27E10 (early inflammatory stage marker), and RM3/1 (healing phase marker), different subpopulations of macrophages were differentiated in surgically removed membranes from patients with macular pucker (n = 6), proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (n = 11), traumatic PVR (n = 19), and proliferative diabetic retinopathy (PDR) (n = 11). Macrophages were predominantly found in traumatic PVR and PDR. Some healing phase (RM3/1) macrophages were detected in all disease entities. Inflammatory stage macrophages (positive staining for 27E10) could not be detected in PVR following rhegmatogenous retinal detachment and idiopathic macular pucker. In traumatic PVR inflammatory stage macrophages were associated with a short history of disease whereas in PDR all types of macrophages could be detected regardless of clinical history and duration of the disease.     

Corneal changes in nine-banded armadillos with leprosy

Leprosy is the third leading cause of blindness worldwide; however, little is known about the ocular changes that occur during the disease process. We have studied the eyes of two nine-banded armadillos with experimental Mycobacterium leprae infection by light and electron microscopy. Both animals had been inoculated intracutaneously, one 5 years and the other 2 years previously. Light microscopy revealed invasion by acid-fast bacilli which were seen in keratocytes and mononuclear phagocytes in all layers of the corneal stroma. In both animals, large macrophage granulomas were observed in the deep stroma, which was vascularized. Acid-fast bacilli were also were found in macrophages and vascular endothelial cells. By electron microscopy, numerous bacilli were found in the keratocytes, macrophages, and Schwann cells of myelinated and unmyelinated axons, and in the endothelial cells of blood vessels. The localization of M. leprae and the presence of inflammatory cells in the ocular tissue of both animals suggest that the bacilli reach the eye by the neural and/or vascular route. One animal showed much more extensive disease and bacillary yield than the other, indicating that ocular involvement may be independent of the generalized infection. Further studies of early ocular involvement in the armadillo and other animals could help to clarify the pathogenesis of this potentially blinding infection.     

龙胆泻肝汤对实验性自身免疫性葡萄膜炎大鼠M1/M2巨噬细胞极化平衡的调控作用

目的 探讨龙胆泻肝汤(Longdan Xiegan decoction,LXD)对实验性自身免疫性葡萄膜炎(EAU)大鼠M1/M2巨噬细胞极化平衡的调控作用.方法 将48只雌性Lewis大鼠随机分为正常对照组、EAU模型组和LXD干预组,其中EAU模型组和LXD干预组大鼠首先诱导并建立EAU模型,LXD干预组大鼠每天给...     

Role of macrophages in uveal melanoma

Tumor-associated macrophages have been related to a worse prognosis for survival in several tumors, among them uveal melanoma. In particular for proangiogenic and anti-inflammatory M2-type macrophages, a contributory role to tumor growth has been described. This study demonstrated that most tumor-associated macrophages in uveal melanoma exhibited the M2-phenotype. Tumors with monosomy 3 that have an unfavorable prognosis exhibited significantly more M2-type macrophages than tumors with disomy of chromosome 3. These findings point to a possible pathophysiologic mechanism that links an inflammatory phenotype in uveal melanoma with structural chromosomal abnormalities such as monosomy 3.     

The role of chemokines and their receptors in uveitis

T-cell-dependent immunological events are increasingly being regarded as extremely important in the pathogenesis of uveitis. Several studies have also shown that macrophages are major effectors of tissue damage in uveitis. Neutrophils are also thought to play a central role in the pathogenesis of Behçet’s disease. Chemokines are a superfamily of 8 to 10-kDa secreted proteins that direct the recruitment of leukocytes to sites of inflammation. The specific biological effects of chemokines are mediated by a family of seven transmembrane-spanning G-protein-coupled receptors. Recent studies of animals and humans suggest that chemokines and their receptors play a key role in leukocyte recruitment into the eye in uveitis. A strategy for blocking chemokines or chemokine receptors could be a new approach for treatment of uveitis.