Veterinary Research Forum
Vet Res Forum

Intra-vitreal injection of methotrexate in experimental endotoxin-induced uveitis in rabbit

Document Type : Original Article

Authors

Mohammad Abbaszadeh Hasiri 1
Effat Baghaei Moghaddam 1
Mohammad Reza Khalili 2
Amin Hossein Amini 1
Masoomeh Eghtedari 2
Mohammad Azizzadeh 3
Hooman Razmi 2

1 Department of Clinical Science, Faculty of Veterinary Medicine, Shiraz University, Shiraz, Iran

2 Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

https://doi.org/10.30466/vrf.2018.33110
Abstract
Uveitis is a major cause of vision loss. Methotrexate (MTX) has been widely used in uveitis due to its relatively safe profile. The purpose of this study was to evaluate the effects of two different dosages of MTX via intra-vitreal administration for treatment of endotoxin induced uveitis (EIU) in an experimental model. Thirty-five healthy rabbits were randomly divided into four groups and all animals were tolerated intra-vitreal injections. The first group received normal saline (NS), the second group received normal saline plus Salmonella typhimurium lipopolysaccharide endotoxin (LPS), (NS+LPS), the third group received 400 μg MTX plus LPS (LPS+MTX 400) and the fourth group received 800 μg MTX plus LPS (LPS+MTX 800). Intra-ocular inflammation was evaluated by clinical examination scoring during 7 post-injection days and histopathological examination at the end of study. Kruskal-Wallis and Mann-Whitney U tests were used to compare the histopathological and clinical scores. According to the clinical examinations, all groups demonstrated higher uveitis score than group 1 on first post-injection day. Also, groups 2 and 3 showed greater uveitis score than group 4. On the third, fifth and seventh post-injection days, clinical uveitis score in groups 2, 3 and 4 was significantly higher than group 1. The mean histopathological inflammation intensity scores in groups 2, 3 and 4 were significantly higher than group 1. Single intra-vitreal injection of 400 μg and 800 μg of MTX did not show significant anti-inflammatory effects on EIU in rabbits.

Keywords

Inflammation
Intra-vitreal injection
Methotrexate
Uveitis
Subjects

  1.  

    1. Durrani O, Tehrani N, Marr J, et al. Degree, duration, and causes of visual loss in uveitis. Br J Ophthalmol 2004; 88(9): 1159-1162.
    2. Durrani O, Meads C, Murray P. Uveitis: A potentially blinding disease. Ophthalmologica 2004; 218(4): 223-236.
    3. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140(3):509-516.
    4. Selmi C. Diagnosis and classification of autoimmune uveitis. Autoimmun Rev2014; 13(4-5): 591-594.
    5. Leung TG, Thorne JE. Emerging drugs for the treatment of uveitis. Expert Opin Emerg Drugs 2013; 18(4): 513-521.
    6. De Vos A, Hoekzema R, Kijlstra A. Cytokines and uveitis, a review. Curr Eye Res 1992; 11(6): 581-597.
    7. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: Recommendations of an expert panel. Am J Ophthalmol 2000; 130(4):
      492-513.
    8. Taylor SR, Habot-Wilner Z, Pacheco P, et al. Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema. Ophthalmology 2009; 116(4): 797-801.
    9. Kulkarni P. Review: Uveitis and immunosuppressive drugs. J Ocul Pharmacol Ther 2001; 17(2): 181-187.
    10. Bachta A, Kisiel B, Tłustochowicz M, et al. High efficacy of methotrexate in patients with recurrent idiopathic acute anterior uveitis: A prospective study. Arch Immunol Ther Exp (Warsz) 2017; 65(1):93-97.
    11. Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. JRheumatol 2005; 32(2): 362-365.
    12. Gangaputra S, Newcomb CW, Liesegang TL, et al. Methotrexate for ocular inflammatory diseases. Ophthalmology 2009; 116(11): 2188-2198. e1.
    13. Kaplan-Messas A, Barkana Y, Avni I, et al. Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis. Ocul Immunol Inflamm 2003; 11(2): 131-139.
    14. Samson CM, Waheed N, Baltatzis S, et al. Methotrexate therapy for chronic noninfectious uveitis: Analysis of a case series of 160 patients. Ophthalmology 2001; 108(6): 1134-1139.
    15. Shah SS, Lowder CY, Schmitt MA, et al. Low-dose methotrexate therapy for ocular inflammatory disease. Ophthalmology 1992; 99(9): 1419-1423.
    16. Bom S, Zamiri P, Lightman S. Use of methotrexate in the management of sight-threatening uveitis. Ocul Immunol Inflamm 2001; 9(1): 35-40.
    17. Munoz-Fernandez S, Garcia-Aparicio AM, Hidalgo MV, et al. Methotrexate: An option for preventing the recurrence of acute anterior uveitis. Eye (Lond) 2009; 23(5): 1130-1133.
    18. Weiss AH, Wallace CA, Sherry DD. Methotrexate for resistant chronic uveitis in children with juvenile rheumatoid arthritis. J Pediatr 1998; 133(2): 266-268.
    19. Statement for the Use of Animals in Ophthalmic and Visual Research. Available at: https://www.opt.uh.edu/ onlinecoursematerials/PHOP6275/2015_Materials/PH
      OP6275_Class3_3_Animals_in_Research_ARVO_Statement.pdf. Accessed Oct 15, 2017.
    20. Oztürk F, Kurt E, Emiroglu L, et al. Effect of propolis on endotoxin-induced uveitis in rabbits. Jpn J Ophthalmol 1999; 43(4): 285-289.
    21. Verma MJ, Mukaida N, Vollmer–Conna U, et al. Endotoxin-induced uveitis is partially inhibited by anti–IL-8 antibody treatment. Invest Ophth Vis Sci 1999; 40(11): 2465-2470.
    22. Farber S, Diamond LK, Mercer RD, et al. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med 1948; 238(23): 787-793.
    23. Cannella AC, O’dell JR. Traditional DMARDs: Methotrexate, lefl unomide, sulfasalazine, hydroxyl-chloroquine, and combination therapies. In: Firestein G, Budd R, Gabriel SE, McInnes IB, O'Dell J (Eds.) Kelley’s Textbook of Rheumatology. 8th ed. Philadelphia, USA: Saunders Elsevier 2008; 2052-2110.
    24. Khalil HEM, Raafat HA, Azab NA, et al. The role of intraocular methotrexate in the management of uveitis and posterior segment involvement in Behçet’s disease patients. Egypt Rheumatol 2015; 37(3): 113-118.
    25. Hardwig PW, Pulido JS, Erie JC, et al. Intraocular methotrexate in ocular diseases other than primary central nervous system lymphoma. Am J Ophthalmol 2006; 142(5): 883-885.
    26. Taylor SR, Banker A, Schlaen A, et al. Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis. Retina 2013; 33(10): 2149-2154.
    27. Eperon S, Balaskas K, Vaudaux J, et al. Experimental uveitis can be maintained in rabbits for a period of six weeks after a safe sensitization method. Curr Eye Res 2013; 38(3): 405-412.
    28. Bae JH, Lee SC. Effect of intravitreal methotrexate and aqueous humor cytokine levels in refractory retinal vasculitis in Behcet disease. Retina 2012;32(7): 1395-1402.
Veterinary Research Forum
Volume 9, Issue 4
Autumn 2018
Pages 315-321

  • Receive Date 12 November 2018

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us