Skip to main content
SpringerLink
Log in

Direct Effects of Bevacizumab on Rat Conjunctival Fibroblast

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Successful cases of treatment of Bevacizumab for preventing scar after trabeculectomy in glaucoma patients encourage us to explore its mechanism. In this study, we primarily isolated conjunctival fibroblast from rat. RT-PCR analysis for the cells implicated that conjunctival fibroblast expressed vascular endothelial growth factor (VEGF) and its receptors. Immunofluorescence staining also showed positive staining for VEGFR-1. Furthermore, growth of fibroblast was significantly inhibited by Bevacizumab at dose of 2.5 mg/ml. Real time PCR results showed after 48 h intervention of 2.5 mg/ml Bevacizumab, the mRNA expressions of VEGF and its receptors decreased compared to the control group (P < 0.05) and Bevacizumab also decreased expression of TGFβ1 and TGFβ2 (P < 0.05). In summary, our finding demonstrated that Bevacizumab could directly act on fibroblast and inhibit VEGF, TGFβ1, and TGFβ2 expression.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Norouzpour, A., & Mehdizadeh, A. (2014). New insights into blindness; mechanical fatigue of optic nerve head in glaucomatous optic neuropathy. Journal of Medical Engineering & Technology, 38(7), 367–371.

    Article  Google Scholar 

  2. Bourne, R. R., Stevens, G. A., White, R. A., Smith, J. L., Flaxman, S. R., Price, H., et al. (2013). Causes of vision loss worldwide, 1990–2010: A systematic analysis. The Lancet Global Health, 1(6), 339–349.

    Article  Google Scholar 

  3. Naruo-Tsuchisaka, A., Maruyama, K., Arimoto, G., & Goto, H. (2014). Incidence of postoperative ptosis following trabeculectomy with Mitomycin C. Journal of Glaucoma. doi:10.1097/IJG.0000000000000174.

  4. De Fendi, L. I., Arruda, G. V., Scott, I. U., & Paula, J. S. (2013). Mitomycin C versus 5-fluorouracil as an adjunctive treatment for trabeculectomy: A meta-analysis of randomized clinical trials. Clinical & Experimental Ophthalmology, 41(8), 798–806.

    Article  Google Scholar 

  5. Palanca-Capistrano, A. M., Hall, J., Cantor, L. B., Morgan, L., Hoop, J., & WuDunn, D. (2009). Long-term outcomes of intraoperative 5-fluorouracil versus intraoperative mitomycin C in primary trabeculectomy surgery. Ophthalmology, 116(2), 185–190.

    Article  PubMed  Google Scholar 

  6. Suzuki, R., Nakayama, M., & Satoh, N. (1999). Three types of retinal bleeding as a complication of hypotony after trabeculectomy. Ophthalmologica, 213(2), 135–138.

    Article  CAS  PubMed  Google Scholar 

  7. Atreides, S. P. A., Skuta, G. L., & Reynolds, A. C. (2004). Wound healing modulation in glaucoma filtering surgery. International Ophthalmology Clinics, 44(2), 61–106.

    Article  PubMed  Google Scholar 

  8. Singh, K., Byrd, S., Egbert, P. R., & Budenz, D. (1998). Risk of hypotony after primary trabeculectomy with antifibrotic agents in a black west African population. Journal of Glaucoma, 7(2), 82–85.

    Article  CAS  PubMed  Google Scholar 

  9. Kumar, I., Staton, C. A., Cross, S. S., Reed, M. W., & Brown, N. J. (2009). Angiogenesis, vascular endothelial growth factor and its receptors in human surgical wounds. British Journal of Surgery, 96(12), 1484–1491.

    Article  CAS  PubMed  Google Scholar 

  10. Wilgus, T. A., Ferreira, A. M., Oberyszyn, T. M., Bergdall, V. K., & Dipietro, L. A. (2008). Regulation of scar formation by vascular endothelial growth factor. Laboratory Investigation, 88(6), 579–590.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Chalam, K. V., Brar, V. S., & Murthy, R. K. (2014). Human ciliary epithelium as a source of synthesis and secretion of vascular endothelial growth factor in neovascular glaucoma. JAMA Ophthalmology, 132(11), 1350–1354.

    Article  PubMed  Google Scholar 

  12. Wang, J., & Harasymowycz, P. (2013). Subconjunctival Bevacizumab injection in glaucoma filtering surgery: A case control series. ISRN Ophthalmology, 14, 384.

    Google Scholar 

  13. Vandewalle, E., Abegão Pinto, L., Van Bergen, T., Spielberg, L., Fieuws, S., Moons, L., et al. (2014). Intracameral bevacizumab as an adjunct to trabeculectomy: A 1-year prospective, randomised study. British Journal of Ophthalmology, 98(1), 73–78.

    Article  PubMed  Google Scholar 

  14. Ryoo, N. K., Lee, E. J., & Kim, T. W. (2013). Regression of iris neovascularization after subconjunctival injection of bevacizumab. Korean Journal of Ophthalmology, 27(4), 299–303.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Freiberg, F. J., Matlach, J., Grehn, F., Karl, S., & Klink, T. (2013). Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy. Clinical Ophthalmology, 7, 1211–1217.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Suh, W., & Kee, C. (2013). The effect of bevacizumab on the outcome of trabeculectomy with 5-Fluorouracil. Journal of Ocular Pharmacology and Therapeutics, 29(7), 646–651.

    Article  CAS  PubMed  Google Scholar 

  17. Rewri, P., Balekudaru, S., Shah, J., George, R., & Lingam, V. (2013). Safety and efficacy of using off-label bevacizumab versus mitomycin C to prevent bleb failure in a single site phacotrabeculectomy by a randomized controlled clinical trial. Journal of Glaucoma, 22(3), 266.

    Article  PubMed  Google Scholar 

  18. Reichel, M. B. (1998). New model of conjunctival scarring in the mouse eye. British Journal of Ophthalmology, 82, 1072–1077.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Ryoo, N. K., Lee, E. J., & Kim, T. W. (2013). Regression of iris neovascularization after subconjunctival injection of bevacizumab. Korean Journal of Ophthalmology, 27(4), 299–303.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Landers, J. (2012). Avastin in glaucoma surgery. Clinical & Experimental Ophthalmology, 40(8), 769–770.

    Article  Google Scholar 

  21. Cardarelli, W. J., & Smith, R. A. (2013). Managed care implications of age-related ocular conditions. The American Journal of Managed Care, 19(5 Suppl), S85–S91.

    PubMed  Google Scholar 

  22. Georgoulas, S., Dahlmann-Noor, A., Brocchini, S., & Khaw, P. T. (2008). Modulation of wound healing during and after glaucoma surgery. Progress in Brain Research, 173, 237–254.

    Article  CAS  PubMed  Google Scholar 

  23. Cordeiro, M. F., Siriwardena, D., Chang, L., & Khaw, P. T. (2000). Wound healing modulation after glaucoma surgery. Current Opinion in Ophthalmology, 11, 121–126.

    Article  CAS  PubMed  Google Scholar 

  24. Desmouliere, A., Geinoz, A., Gabbiani, F., & Gabbiani, G. (1993). Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. Journal of Cell Biology, 122, 103–111.

    Article  CAS  PubMed  Google Scholar 

  25. Park, H. Y., Kim, J. H., & Park, C. K. (2013). VEGF induces TGF-β1 expression and myofibroblast transformation after glaucoma surgery. American Journal of Pathology, 182(6), 2147–2154.

    Article  CAS  PubMed  Google Scholar 

  26. Wang, L., Kwak, J. H., Kim, S. I., He, Y., & Choi, M. E. (2004). Transforming growth factor-beta1 stimulates vascular endothelial growth factor 164 via mitogen-activated protein kinase kinase 3-p38alpha and p38delta mitogen-activated protein kinase-dependent pathway in murine mesangial cells. Journal of Biological Chemistry, 279, 33213–33219.

    Article  CAS  PubMed  Google Scholar 

  27. Lee, K. S., Park, S. J., Kim, S. R., Min, K. H., Lee, K. Y., Choe, Y. H., et al. (2008). Inhibition of VEGF blocks TGFbeta1 production through a PI3 K/Akt signalling pathway. European Respiratory Journal, 31, 523–531.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Gangwei Cheng & Jialiang Zhao

  2. International Medical Center, Chinese PLA General Hospital, Beijing, China

    Hang Xiang

  3. Department of Ophthalmology, Hebei Provincial Ophthalmic Hospital, Hebei, China

    Guoxing Yang

  4. Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

    Jianmin Ma

Authors
  1. Gangwei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hang Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guoxing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianmin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jialiang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jialiang Zhao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, G., Xiang, H., Yang, G. et al. Direct Effects of Bevacizumab on Rat Conjunctival Fibroblast. Cell Biochem Biophys 73, 45–50 (2015). https://doi.org/10.1007/s12013-015-0565-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-015-0565-0

Keywords

Search

Navigation