LX211 (voclosporin) suppresses experimental uveitis and inhibits human T cells

Investigative Ophthalmology and Visual Science

Volumn 50, Issue 1, 2009, Pages 249-255

  Cunningham, Matthew A ^a   Austin, Bobbie Ann ^a   Li, Zhuqing ^a   Liu, Baoying ^a   Yeh, Steven ^a   Chan, Chi Chao ^a   Anglade, Eddy ^b   Velagaleti, Poonam ^b   Nussenblatt, Robert B ^a  

^a NATIONAL EYE INSTITUTE   (United States)

^b Lux Biosciences Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCINEURIN INHIBITOR; CYCLOSPORIN A; CYTOKINE; LX 211; UNCLASSIFIED DRUG; VOCLOSPORIN; CYCLOSPORIN; EYE PROTEIN; IMMUNOSUPPRESSIVE AGENT; INTERPHOTORECEPTOR RETINOID BINDING PROTEIN; INTERSTITIAL RETINOL-BINDING PROTEIN; RETINOL BINDING PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN SPECIFICITY; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DRUG INHIBITION; DRUG MEGADOSE; EFFECTOR CELL; ENUCLEATION; HISTOPATHOLOGY; IMMUNIZATION; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; LYMPH NODE; LYMPHOCYTE PROLIFERATION; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; SCORING SYSTEM; T LYMPHOCYTE; TREATMENT OUTCOME; UVEITIS; ANIMAL; AUTOIMMUNE DISEASE; CHEMICALLY INDUCED DISORDER; DISEASE MODEL; DRUG EFFECT; HUMAN; IMMUNOLOGY; LEWIS RAT; LYMPHOCYTE ACTIVATION; METABOLISM; RETINITIS; SUBCUTANEOUS DRUG ADMINISTRATION;

ANIMALS; AUTOIMMUNE DISEASES; CYCLOSPORINE; CYTOKINES; DISEASE MODELS, ANIMAL; EYE PROTEINS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INJECTIONS, SUBCUTANEOUS; LYMPHOCYTE ACTIVATION; MALE; RATS; RATS, INBRED LEW; RETINITIS; RETINOL-BINDING PROTEINS; T-LYMPHOCYTES; TREATMENT OUTCOME; UVEITIS;

EID: 58249094500     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.08-1891     Document Type: Article

References (37)

1. Suttorp-Schulten MS, Rothova A. The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol. 1996;80:844-848.
2. Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: Fundamentals and Clinical Practice. 2nd ed. St. Louis: Mosby; 1996.
3. Kulkarni P. Review: uveitis and immunosuppressive drugs. J Ocul Pharmacol Ther. 2001;17:181-187.
4. Hogan AC, McAvoy CE, Dick AD, Lee RW. Long-term efficacy and tolerance of tacrolimus for the treatment of uveitis. Ophthalmology. 2007;114(5):1000-1006.
5. Nussenblatt RB, Palestine AG, Chan CC. Cyclosporine therapy for uveitis: long-term follow-up. J Ocul Pharmacol. 1985;1(4):369-382.
6. BenEzra D, Cohen E, Rakotomalala M, et al. Treatment of endogenous uveitis with cyclosporine A. Transplant Proc. 1988;20:122-127.
7. Sloper CM, Powell RJ, Dua HS. Tacrolimus (FK506) in the treatment of posterior uveitis refractory to cyclosporine. Ophthalmology. 1999;106(4):723-728.
8. Walton RC, Nussenblatt RB, Whitcup SM. Cyclosporine therapy for severe sight-threatening uveitis in children and adolescents. Ophthalmology. 1998;105(11):2028-2034.
9. Whitcup SM, Salvo EC Jr, Nussenblatt RB. Combined cyclosporine and corticosteroid therapy for sight-threatening uveitis in Behçet's disease. Am J Ophthalmol. 1994;118(1):39-45.
10. Wang Y, Ogawa Y, Dogru M, et al. Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease. Bone Marrow Transplant. 2007; 41(3):293-302.
11. Foulks GN. Topical cyclosporine for treatment of ocular surface disease. Int Ophthalmol Clin. 2006;46(4):105-122.
12. Cardenas ME, Zhu D, Heitman J. Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin. Curr Opin Nephrol Hypertens. 1995;4(6):472- 477.
13. Su Q, Weber L, Le Hir M, et al. Nephrotoxicity of cyclosporin A and FK506: inhibition of calcineurin phosphatase. Ren Physiol Biochem. 1995;18(3):128 -139.
14. Redondo-Horcajo M, Lamas S. Oxidative and nitrosative stress in kidney disease: a case for cyclosporine A. J Nephrol. 2005;18(4): 453-457.
15. Serkova NJ, Christians U, Benet LZ. Biochemical mechanisms of cyclosporine neurotoxicity. Mol Interv. 2004;4(2):97-107.
16. Henke W, Nickel E, Jung K. Cyclosporine A inhibits ATP net uptake of rat kidney mitochondria. Biochem Pharmacol. 1992; 43(5):1021-1024.
17. Aspeslet L, Freitag D, Trepanier D, et al. ISA(TX)247: a novel calcineurin inhibitor. Transplant Proc. 2001;33(1-2):1048-1051.
18. Birsan T, Dambrin C, Freitag DG, et al. The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro. Transpl Int. 2005;17(12):767-771.
19. Stalder M, Birsan T, Hubble RW, et al. In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates. J Heart Lung Transplant. 2003;22(12):1343-1352.
20. Gregory CR, Kyles AE, Bernsteen L, et al. Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model. Transplantation. 2004;78(5):681-685.
21. Abel MD, Aspeslet LJ, Freitag DG, et al. ISATX247: a novel calcineurin inhibitor. J Heart Lung Transplant. 2001;20(2):161.
22. Anglade E, Yatscoff R, Foster R, Grau U. Next-generation calcineurin inhibitors for ophthalmic indications. Expert Opin Investig Drugs. 2007;16(10):1525-1540.
23. Bissonnette R, Papp K, Poulin Y, et al. A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2006;54(3): 472-478.
24. Oh-i K, Keino H, Goto H, et al. Intravitreal injection of tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats. Br J Ophthalmol. 2007;91(2):237-242.
25. Ni M, Chan CC, Nussenblatt RB, Mochizuki M. FR900506 (FK506) and 15-deoxyspergualin (15-DSG) modulate the kinetics of infiltrating cells in eyes with experimental autoimmune uveoretinitis. Autoimmunity. 1990;8(1):43-51.
26. Kawashima H, Fujino Y, Mochizuki M. Effects of a new immunosuppressive agent, FK506, on experimental autoimmune uveoretinitis in rats. Invest Ophthalmol Vis Sci. 1988;29(8):1265-1271.
27. Mochizuki M, Nussenblatt RB, Kuwabara T, Gery I. Effects of cyclosporine and other immunosuppressive drugs on experimental autoimmune uveoretinitis in rats. Invest Ophthalmol Vis Sci. 1985;26(2):226 -232.
28. Nussenblatt RB, Rodrigues MM, Wacker WB, et al. Cyclosporin a: inhibition of experimental autoimmune uveitis in Lewis rats. J Clin Invest. 1981;67(4):1228-1231.
29. Redmond TM, Wiggert B, Robey FA, et al. Isolation and characterization of monkey interphotoreceptor retinoid-binding protein, a unique extracellular matrix component of the retina. Biochemistry. 1985;24:787-793.
30. Pepperberg DR, Okajima TL, Ripps H, et al. Functional properties of interphotoreceptor retinoid-binding protein. Photochem Photobiol. 1991;54(6):1057-1060.
31. Agarwal RK, Caspi RR. Rodent models of experimental autoimmune uveitis. Methods Mol Med. 2004;102:395-419.
32. Chan CC, Caspi RR, Ni M, et al. Pathology of experimental autoimmune uveoretinitis in mice. J Autoimmun. 1990;3(3):247-255.
33. Maksymowych WP, Jhangri GS, Aspeslet L, et al. Amelioration of accelerated collagen induced arthritis by a novel calcineurin inhibitor, ISA(TX)247. J Rheumatol. 2002;29(8):1646-1652.
34. Amadi-Obi A, Yu CR, Liu X, et al. Th17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med. 2007;13(6):711-718.
35. Murray PI, Clay CD, Mappin C, Salmon M. Molecular analysis of resolving immune responses in uveitis. Clin Exp Immunol. 1999; 117(3):455- 461.
36. +) T cell phenotype and activation status in intermediate uveitis. Br J Ophthalmol. 2004;88(3):412- 416.
37. Luger D, Silver PB, Tang J, et al. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med. 2008;205(4):799-810.