scholarly journals A Cell Penetrating Peptide from SOCS-1 Prevents Ocular Damage in Experimental Autoimmune Uveitis

2018 ◽  
Author(s):  
Chulbul M. Ahmed ◽  
Michael T. Massengill ◽  
Cristhian J. Ildefonso ◽  
Howard M. Johnson ◽  
Alfred S. Lewin
Keyword(s):  
Adaptor Protein ◽  
Barrier Properties ◽  
Topical Administration ◽  
List Type ◽  
Potential Candidate ◽  
Experimental Autoimmune Uveitis ◽  
Autoimmune Uveitis ◽  
Inhibitory Region ◽  
Kinase Inhibitory Region ◽  
Experimental Autoimmune

AbstractWe describe an immunosuppressive peptide corresponding to the kinase inhibitory region (KIR) of the intracellular checkpoint protein suppressor of cytokine signaling 1 (SOCS-1) that binds to the phospho-tyrosine containing regions of the tyrosine kinases JAK2 and TYK2 and the adaptor protein MAL, and thereby inhibits signaling downstream from these signaling mediators. The peptide, SOCS1-KIR, is thus capable of downregulating overactive JAK/STAT or NF-kB signaling in somatic cells, including those in many compartments of the eye. Attachment of poly-arginine to this peptide (R9-SOCS1-KIR) allows it to penetrate the plasma membrane in aqueous media. R9-SOCS1-KIR was tested in ARPE-19 cells and was found to attenuate mediators of inflammation by blocking the inflammatory effects of IFNγ, TNFα, or IL-17A. R9-SOCS1-KIR also protected against TNFα or IL-17A mediated damage to the barrier properties of ARPE-19 cells, as evidenced by immunostaining with the tight junction protein, zona occludin 1 (ZO-1), and measurement of transepithelial electrical resistance (TEER). Experimental autoimmune uveitis (EAU) was generated in B10.RIII mice using a peptide of interphotoreceptor retinal binding protein (IRBP161-180) as immunogen. Topical administration of R9-SOCS1-KIR protected ocular structure and function as seen by fundoscopy, optical coherence tomography (OCT), and electroretinography (ERG). The ability R9-SOCS1-KIR to suppress ocular inflammation and preserve barrier properties of retinal pigment epithelium makes it a potential candidate for aqueous treatment of autoimmune uveitis.Highlightspeptide corresponding to the kinase inhibitory region of SOCS-1 linked to poly-arginine (R9-SOCS1-KIR) and its inactive control peptide were chemically synthesized.R9-SOCS1-KIR attenuated pro-inflammatory effects of IFNγ, TNFα, and IL-17 in ARPE-19 cells, thus showing a simultaneous inhibition Th1 and Th17 cell functions.Damage to barrier properties of ARPE-19 cells caused by TNFα or IL-17 was prevented in the presence of R9-SOCS1-KIR.Topical administration of R9-SOCS1-KIR prevented ocular damage in a mouse model of experimental autoimmune uveitis.

scholarly journals Preventive effect of chrysin on experimental autoimmune uveitis triggered by injection of human IRBP peptide 1–20 in mice

2016 ◽  
Vol 14 (8) ◽  
pp. 702-711 ◽  
Author(s):  
Xiangda Meng ◽  
Sijie Fang ◽  
Zhuhong Zhang ◽  
Yang Wang ◽  
Caiyun You ◽  
...  
Keyword(s):  
Preventive Effect ◽  
Experimental Autoimmune Uveitis ◽  
Autoimmune Uveitis ◽  
Experimental Autoimmune

OP0258 Experimental Autoimmune Uveitis in Mice Lacking TNF Receptors

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 169.2-169
Author(s):  
C. Iwahashi ◽  
M. Fujimoto ◽  
Y. Takahashi ◽  
T. Ohkawara ◽  
S. Serada ◽  
...  
Keyword(s):  
Tnf Receptors ◽  
Experimental Autoimmune Uveitis ◽  
Autoimmune Uveitis ◽  
Experimental Autoimmune

scholarly journals Regulation of experimental autoimmune uveitis in rats-separation of MHC and non-MHC gene effects

1991 ◽  
Vol 86 (3) ◽  
pp. 419-425 ◽  
Author(s):  
S. HIROSE ◽  
K. OGASAWARA ◽  
T. NATORI ◽  
Y. SASAMOTO ◽  
S. OHNO ◽  
...  
Keyword(s):  
Experimental Autoimmune Uveitis ◽  
Gene Effects ◽  
Autoimmune Uveitis ◽  
Experimental Autoimmune

Allopurinol has Immunomodulating Activity following Topical and Systemic Application in Experimental Autoimmune Uveitis

2001 ◽  
Vol 11 (3) ◽  
pp. 252-260 ◽  
Author(s):  
F.H. Grus ◽  
A.J. Augustin ◽  
K. Loeffler ◽  
B. Dick ◽  
J. Lutz ◽  
...  
Keyword(s):  
Topical Application ◽  
Systemic Treatment ◽  
Sodium Dodecyl ◽  
Radical Scavenging ◽  
Topical Steroids ◽  
Immunomodulating Effect ◽  
Experimental Autoimmune Uveitis ◽  
Western Blots ◽  
Autoimmune Uveitis ◽  
Experimental Autoimmune

Purpose Allopurinol has beneficial effects in the systemic treatment of lens-induced uveitis and experimental autoimmune uveitis (EAU). This is believed to be due to a reduction of oxidative tissue damage through its dose-dependent free radical scavenging ability, and to an immunomodulating effect. The purpose of this study was to demonstrate the immunological effects on the IgG-antibody repertoire in EAU after topical and systemic allopurinol and steroids. Methods We assigned 43 male Lewis rats to 6 different groups: healthy rats (BASE, n=3), EAU without therapy (CTRL, n=9); systemic treatment with allopurinol (ALSYS, n=9, 50 mg/kg body wt.i.v., given every three days for two weeks), topical allopurinol (ALLOC, n=6, 8 times/day), systemic methylprednisolone (STSYS, n=10, 7.5 mg/kg body wt. i.v. (Hoechst, Frankfurt, Germany)), and topical treatment with prednisolone acetate 1% (Inflanefran Forte®) (STLOC, n=6). Sera were tested against Western blots (WB) of SDS-PAGE (sodium-dodecyl-sulfate polyacrylamide-gelelectorphoresis) of retinal proteins. Based on digital image analysis, discriminance was analysed. Results The analysis of discriminance indicated that all therapy groups were significantly different from untreated controls (Wilks' lambda = 0.174; p<0.01). Comparing only the number of peaks and the intensities, the WB of allopurinol treated animals showed a much stronger, significant, immunomodulating effect than those treated with steroids (p>0.05), even after topical application (p<0.01). Conlcusions Allopurinol had an immunomodulating effect in EAU. Surprisingly, the topical application had more effect than systemically applied allopurinol. Allopurinol had stronger effects than systemic or topical steroids. Allopurinol appears to offer promise in the treatment of uveitis. Topical application of the drug helps to reduce possible complications such as the allopurinol hypersensitivity syndrome.

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