Skip to main content
SpringerLink
Log in

The active metabolite of leflunomide A771726 inhibits corneal neovascularization

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

The effects of A771726, the active metabolite of leflunomide, on experimental rat corneal neovascularization (NV) in vivo and on cultured human umbilical vein endothelial cells in vitro were studied. The corneal NV was induced by alkali burn in 40 SD rats. The rats were randomly divided into 4 groups with 10 rats in each group. Group A was treated with 0.9% sodium chloride (control group), and group B, group C and group D were given different concentrations of A771726 eye drops (0.5%, 1.0%, 2.0% respectively) 4 times daily during days 0–28. The occurrence and development of corneal NV were observed at 4, 7, 14, 21 and 28 day after alkali burn by a slit lamp microscope. The cultured human umbilical vein endothelial cells (ECV-304) were incubated with A771726 solution at different concentrations (20, 40, 80, 160, 320 mol/L) for 36 h. The proliferation of cells was assessed by methyl thiazolyl tetrazolium (MTT), and the expression of proliferating cell nuclear antigen (PCNA) in cells was detected by using immunofluorescence under the laser confocal microscope. The rat model showed that the onset of corneal NV was delayed and progression of corneal NV was inhibited in the groups C and D. The corneal NV areas in groups C and D were significantly smaller than in groups A and B (P<0.01). No significant difference was found in corneal NV areas between groups C and group D (P>0.05). A771726 solution (⩾40 μmol/L) could inhibit proliferation of human umbilical vein endothelial cells and decrease the expression of PCNA in cells significantly. A771726, as the active metabolite of leflunomide, strongly prevented corneal NV induced by alkali burn in the in vivo model, and inhibited proliferation of human umbilical vein endothelial cells in the in vitro model. Therefore, A771726 may serve as an angiogenic inhibitor in the treatment of corneal NV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. De Freitas A M, Melo B C, Mendonca C N et al. Causes and risk factors for graft failure in surgeries performed by physicians in fellowship training. Cornea, 2006, 25(3):251–256

    Article  PubMed  Google Scholar 

  2. McChesney L P, Xiao F, Sankary H N et al. An evaluation of leflunomide in the canine renal transplantation model. Transplantation, 1994,57(12):1717–1722

    PubMed  CAS  Google Scholar 

  3. Williams J W, Mital D, Chong A et al. Experiences with leflunomide in solid organ transplantation. Transplantation, 2002,73(3):358–366

    Article  PubMed  CAS  Google Scholar 

  4. Seo K, Choi J, Park M et al. Angiogenesis effects of nerve growth factor (NGF) on rat corneas. J Vet Sci, 2001,2(2):125–130

    PubMed  CAS  Google Scholar 

  5. Rossant J, Howard L. Signaling pathways in vascular development. Annu Rev Cell Dev Biol, 2002,18(2):541–573

    Article  PubMed  CAS  Google Scholar 

  6. Kirsch B M, Zeyda M, Stuhlmeier K et al. The active metabolite of leflunomide, A771726, interferes with dendritic cell function. Arthritis Res Ther, 2005,7(3):694–703

    Article  Google Scholar 

  7. Fox R L, Herrmann M L, Franqou C G et al. Mechanism of action for leflunomide in rheumatoid arthritis. Clin Immunol, 1999,93(3):198–208

    Article  PubMed  CAS  Google Scholar 

  8. Shawver L K, Schwartz D P, Mann E et al. Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-(trifluoromethyl)-phenyl]5-methylisoxazole-4-carboxamide. Clin Cancer Res, 1997,3(7):1167–1177

    PubMed  CAS  Google Scholar 

  9. Philipp W, Speicher L, Humpel C. Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas. Invest Ophthalmol Vis Sci, 2000,41(9):2514–2522

    PubMed  CAS  Google Scholar 

  10. Claesson-Welsh L. Signal transduction by vascular endothelial growth factor receptors. Biochem Soc Trans, 2003,31(Pt1):20–24

    PubMed  CAS  Google Scholar 

  11. Urushibara M, Takayanagi H, Koga T et al. The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kappa B ligand-stimulated induction of nuclear factor of activated T cells cl. Arthritis Rheum, 2004,50(3):794–804

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Mingchang Zhang  (张明昌), Nian Hao  (郝 念) & Fang Bian  (边 芳)

Authors
  1. Mingchang Zhang  (张明昌)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nian Hao  (郝 念)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fang Bian  (边 芳)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mingchang Zhang  (张明昌).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, M., Hao, N. & Bian, F. The active metabolite of leflunomide A771726 inhibits corneal neovascularization. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 28, 364–368 (2008). https://doi.org/10.1007/s11596-008-0332-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-008-0332-1

Key words

Search

Navigation