Down-regulation of inducible co-stimulator (ICOS) by intravitreal injection of small interfering RNA (siRNA) plasmid suppresses ongoing experimental autoimmune uveoretinitis in rats

Hou, Yongzhong; Lin, Xiaobo; Fu, Shaoying; Zhang, Xiaoning; Liu, Jingjing; Liu, Hongling; Lv, Bingjie; Cui, Hao

doi:10.1007/s00417-008-1023-0

Cited by 11 publications

(5 citation statements)

References 32 publications

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“…Other approaches such as Amino acid copolymers [173], siRNA against inducible co-stimulator (ICOS) [174], IL-1 receptor agonist [175], Dexamethasone [176], angiotensin II type 1 receptor blocker Telmisartan [177, 178], glucosamine [179], vaclosporin (LX211) [180], chitinase inhibitors [181], vascular adhesion protein-1 inhibitors [182], methylprednisolone acetate [183], cloricromene, a coumarin derivative [184], vasoactive intestinal peptide-loaded liposomes [185], oligodeoxynucleotide [186], DAF [187] and gene therapy [190] have been shown to contain inflammation in the experimental model of uveitis. Most of these experimental studies present an opportunity to explore novel therapeutic methods for uveitis, which includes sight-threatening diseases such as Behcet disease, birdshot retinochoroidopathy, Vogt- Koyanagi-Harada, sympathetic ophthalmia and ocular sarcoidosis.…”

Section: Antioxidant Treatments For Uveitismentioning

confidence: 99%

Emerging Role of Antioxidants in the Protection of Uveitis Complications

Yadav

Kalariya

Ramana³

2011

CMC

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Current understanding of the role of oxidative stress in ocular inflammatory diseases indicates that antioxidant therapy may be important to optimize the treatment. Recently investigated antioxidant therapies for ocular inflammatory diseases include various vitamins, plant products and reactive oxygen species scavengers. Oxidative stress plays a causative role in both non-infectious and infectious uveitis complications, and novel strategies to diminish tissue damage and dysfunction with antioxidant therapy may ameliorate visual complications. Preclinical studies with experimental animals and cell culture demonstrate significance of anti-inflammatory effects of a number of promising antioxidant agents. Many of these antioxidants are under clinical trial for various inflammatory diseases other than uveitis such as cardiovascular, rheumatoid arthritis and cancer. Well planned interventional clinical studies of the ocular inflammation will be necessary to sufficiently investigate the potential medical benefits of antioxidant therapies for uveitis. This review summarizes the recent investigation of novel antioxidant agents for ocular inflammation, with selected studies focused on uveitis.

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Section: Antioxidant Treatments For Uveitismentioning

confidence: 99%

Emerging Role of Antioxidants in the Protection of Uveitis Complications

Yadav

Kalariya

Ramana³

2011

CMC

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“…RNAi is a process whereby double-stranded RNA induces sequence-specific degradation of homologous mRNA [ 13 ]. The main diseases treated using RNAi gene therapy include hepatitis B, human immunodeficiency virus (HIV) infection [ 14 ], cancer [ 15 , 16 ], neurodegenerative disorders [ 17 ], ocular diseases [ 18 ], respiratory diseases [ 19 ], and arthritis [ 20 ]. We have previously described the feasibility of silence HLA class I and class II expression using RNAi technology [ 21 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

MHC Universal Cells Survive in an Allogeneic Environment after Incompatible Transplantation

Figueiredo

Wedekind

Müller

et al. 2013

BioMed Research International

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Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC) diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m) was delivered into fibroblasts derived from LEW/Ztm (RT1l) (RT1-Al) rats using a lentiviral-based vector. MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously in LEW rats (RT1l) and MHC-congenic LEW.1W rats (RT1u), respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine.

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“…Accordingly, regulation of cosignals can be used in the treatment of autoimmune diseases, and clinical drugs (e.g., CTLA4-Ig for psoriasis and rheumatoid arthritis) have been developed based on this principle. In EAU, ICOS expression has been reported to be upregulated, and attenuation of ICOS function has been shown to reduce the disease severity (39,40). The therapeutic potential of CTLA4-Ig in EAU was also demonstrated (41).…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Function of Herpesvirus Entry Mediator in Experimental Autoimmune Uveitis by Induction of Th1- and Th17-Type T Cell Responses

Sakoda

Nagai

Murata

et al. 2016

The Journal of Immunology

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Herpesvirus entry mediator (HVEM), a member of the TNFR superfamily, serves as a unique molecular switch to mediate both stimulatory and inhibitory cosignals, depending on its functions as a receptor or ligand interacting with multiple binding partners. In this study, we explored the cosignaling functions of HVEM in experimental autoimmune uveitis (EAU), a mouse model resembling human autoimmune uveitis conditions such as ocular sarcoidosis and Behcet disease. Our studies revealed that EAU severity significantly decreased in HVEM-knockout mice compared with wild-type mice, suggesting that stimulatory cosignals from the HVEM receptor are predominant in EAU. Further studies elucidated that the HVEM cosignal plays an important role in the induction of both Th1- and Th17-type pathogenic T cells in EAU, including differentiation of IL-17–producing αβ+γδ− conventional CD4+ T cells. Mice lacking lymphotoxin-like, inducible expression, competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT), B- and T-lymphocyte attenuator (BTLA) or both LIGHT and BTLA are also less susceptible to EAU, indicating that LIGHT–HVEM and BTLA–HVEM interactions, two major molecular pathways mediating HVEM functions, are both important in determining EAU pathogenesis. Finally, blocking HVEM cosignals by antagonistic anti-HVEM Abs ameliorated EAU. Taken together, our studies revealed a novel function of the HVEM cosignaling molecule and its ligands in EAU pathogenesis through the induction of Th1- and Th17-type T cell responses and suggested that HVEM-related molecular pathways can be therapeutic targets in autoimmune uveitis.

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Down-regulation of inducible co-stimulator (ICOS) by intravitreal injection of small interfering RNA (siRNA) plasmid suppresses ongoing experimental autoimmune uveoretinitis in rats

Abstract: Intravitreal injection of siRNA plasmid targeting ICOS effectively down-regulated the expression of ICOS, and was highly effective in suppressing the ongoing process of EAU without any side-effects on systemic cellular immunity.

Cited by 11 publications

References 32 publications

Emerging Role of Antioxidants in the Protection of Uveitis Complications

Emerging Role of Antioxidants in the Protection of Uveitis Complications

MHC Universal Cells Survive in an Allogeneic Environment after Incompatible Transplantation

Pathogenic Function of Herpesvirus Entry Mediator in Experimental Autoimmune Uveitis by Induction of Th1- and Th17-Type T Cell Responses

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