Biological agents for the treatment of uveitis

Servat, Juan Javier; Mears, Katrina A; Black, Evan H.; Huang, John J.

doi:10.1517/14712598.2012.658366

Cited by 32 publications

(17 citation statements)

References 151 publications

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“…Multiple publications describe the effectiveness of biologic agents in patients with recalcitrant posterior uveitis, including drugs directed against lymphocyte markers, tumor necrosis factor alpha, and interleukin-2 (Servat et al, 2012). On the other hand, a number of these agents have been associated with serious systemic toxicities, including potentially fatal infections and progressive multifocal leukoencephalopathy.…”

Section: Clinical Significance Of the Retinal Vascular Diseasesmentioning

confidence: 99%

Role of the retinal vascular endothelial cell in ocular disease

Bharadwaj

Appukuttan

Wilmarth

et al. 2013

Progress in Retinal and Eye Research

137

114

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Retinal endothelial cells line the arborizing microvasculature that supplies and drains the neural retina. The anatomical and physiological characteristics of these endothelial cells are consistent with nutritional requirements and protection of a tissue critical to vision. On the one hand, the endothelium must ensure the supply of oxygen and other nutrients to the metabolically active retina, and allow access to circulating cells that maintain the vasculature or survey the retina for the presence of potential pathogens. On the other hand, the endothelium contributes to the blood-retinal barrier that protects the retina by excluding circulating molecular toxins, microorganisms, and pro-inflammatory leukocytes. Features required to fulfill these functions may also predispose to disease processes, such as retinal vascular leakage and neovascularization, and trafficking of microbes and inflammatory cells. Thus, the retinal endothelial cell is a key participant in retinal ischemic vasculopathies that include diabetic retinopathy and retinopathy of prematurity, and retinal inflammation or infection, as occurs in posterior uveitis. Using gene expression and proteomic profiling, it has been possible to explore the molecular phenotype of the human retinal endothelial cell and contribute to understanding of the pathogenesis of these diseases. In addition to providing support for the involvement of well-characterized endothelial molecules, profiling has the power to identify new players in retinal pathologies. Findings may have implications for the design of new biological therapies. Additional progress in this field is anticipated as other technologies, including epigenetic profiling methods, whole transcriptome shotgun sequencing, and metabolomics, are used to study the human retinal endothelial cell.

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Section: Clinical Significance Of the Retinal Vascular Diseasesmentioning

confidence: 99%

Role of the retinal vascular endothelial cell in ocular disease

Bharadwaj

Appukuttan

Wilmarth

et al. 2013

Progress in Retinal and Eye Research

137

114

View full text Add to dashboard Cite

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“…A wide range of systemic and ocular complications associated with long-term usage of corticosteroids and immunosuppressive medications has pushed the development of new therapies to decrease the burden of these traditional immunosuppressive agents on patients with refractive uveitis. Biologics, also known as cytokine inhibitors, targeting specific mediators of the immuneinflammatory system potentially offer a safer profile and faster response than traditional immunosuppressive agents [1]. However, as human uveitis is highly heterogeneous, with a wide spectrum of disorders, targeting one specific mediator [such as tumour necrosis factor (TNF) or interleukin (IL)-1] does not necessarily apply to all cases.…”

Section: Introductionmentioning

confidence: 99%

The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis

Yuan

Ren

et al. 2013

Clinical and Experimental Immunology

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SummaryMesenchymal stem cells (MSCs) are being explored extensively as a promising treatment for autoimmune diseases. We have recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we examined further the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on T helper type 1 (Th1) and Th17 cells and how long the inhibitory effect lasted, in order to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs decreased the production of Th1 and Th17 cytokines significantly, while the production of Th2 and regulatory T cell (Treg) cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-b] was elevated during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humour (AqH) were reduced in MSC-treated rats. Moreover, the ratio of Th17/Treg cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can regulate negatively both Th1 and Th17 responses and restore the balance of Th17/Tregs in the whole course of EAU, which is important for the regression of the disease.

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“…Thus, the refractory autoimmune disease is considered a tremendous challenge for treatment. The conventional treatment of uveitis includes corticosteroids, immunosuppressive agents and biologics2. However, serious potential side effects limit their use.…”

mentioning

confidence: 99%

AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways

Qiu

Tao

Zheng

et al. 2016

Sci Rep

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Renin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases. With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1–7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established. This axis is emerging as a novel target to attenuate ocular inflammation. However, the underlying molecular mechanisms remain unclear. We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses. Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected. These effects were mediated by activating the Ang-(1–7)/Mas and inhibiting the MAPK, NF-κB and STAT3 signaling pathways. This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1–7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases.

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Biological agents for the treatment of uveitis

Abstract: There are a wide variety of new and emerging biological agents currently being used in the treatment of uveitis which has expanded the therapeutic horizons far beyond previous limitations.

Cited by 32 publications

References 151 publications

Role of the retinal vascular endothelial cell in ocular disease

Role of the retinal vascular endothelial cell in ocular disease

The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis

AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways

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