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Bevacizumab cured age-related macular degeneration (AMD) via down-regulate TLR2 pathway

  • Research Article
  • Published:
Central European Journal of Biology

Abstract

AMD is the main cause of visual impairment in people over 50 years of age and the most common cause of blindness. In recent years, the use of bevacizumab to treat neovascular AMD has become a preferred treatment in the United States. However, whether bevacozumab is available for RPE or AMD patients is unknown. We firstly indicate that Pam3CSK4 (P3C) activates TLR2 pathway during ARPE-19 apoptosis as determined by western blotting. And then, the expression of MyD88, NF-κB, p-IKK in primary RPE cells from AMD patients is significantly down-regulated after treatment with 50 µg L−1 Bevacizumab. Therefore, our data shows that MyD88 is involved in the TLR2 pathway in ARPE-19 cell apoptosis resulting from Pam3CSK4 (P3C). And more importantly, our findings suggested that Bevacizumab cured age-related macular degeneration (AMD) via down-regulate Toll—like receptor 2 (TLR2) pathway in RPE from AMD patients.

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Abbreviations

AMD:

Age-related macular degeneration

RPE:

Retinal pigment epithelium

TLR2:

The mammalian toll like receptor 2

P3C:

Pam3CSK4

References

  1. Martin D.F., Maguire M.G., Ying G.S., Grunwald J.E., Fine S.L., Jaffe G.J., Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration, N. Engl. J. Med., 2011, 364, 1897–1908

    Article  CAS  PubMed  Google Scholar 

  2. Jager R.D., Mieler W.F., Miller J.W., Age-related macular degeneration, N. Engl. J. Med., 2008, 358, 2606–2617

    Article  CAS  PubMed  Google Scholar 

  3. Cipriani V., Matharu B.K., Khan J.C., Shahid H., Stanton C.M., Hayward C., et al., Genetic variation in complement regulators and susceptibility to agerelated. macular degeneration, Immunobiology, 2012, 217, 158–161

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Hurwitz H., Fehrenbacher L., Novotny W., Cartwright T., Hainsworth J., Heim W., et al., Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer, N. Engl. J. Med., 2004, 350, 2335–2342

    Article  CAS  PubMed  Google Scholar 

  5. Meyer C.H., Holz F.G., Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab, Eye (Lond), 2011, 25, 661–672

    Article  CAS  Google Scholar 

  6. Luo Y., Zhuo Y., Fukuhara M., Rizzolo L.J., Effects of culture conditions on heterogeneity and the apical junctional complex of the ARPE-19 cell line, Invest. Ophthalmal. Vis. Sci., 2006, 47, 3644–3655

    Article  Google Scholar 

  7. Hageman G.S., Mullins R.F., Molecular composition of drusen as related to substructural phenotype, Mol. Vis., 1999, 3, 25–28

    Google Scholar 

  8. Algvere P.V., Seregard S., Drusen maculopathy: a risk factor for AMD. Can we prevent visual loss?, Acta Ophthalmol. Scand., 2003, 81, 427–429

    Article  PubMed  Google Scholar 

  9. Bok D., New insights and new approaches toward the study of age-related macular degeneration, Proc. Natl. Acad. Sci. U.S.A., 2002, 99, 14619–14621

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. An E., Lu X., Flippin J., Devaney J.M., Halligan B., Hoffman E.P., et al., Secreted Proteome Profiling in Human RPE Cell Cultures Derived from Donors with Age Related Macular Degeneration and Age Matched Healthy Donors, J. Proteome. Res., 2006, 5, 2599–2610

    Article  CAS  PubMed  Google Scholar 

  11. Uh A., Simmons C.F., Bresee C., Khoury N., Gombart A.F., Nicholson R.C., et al., MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line, Reprod. Biol. Endocrinol., 2009, 7, 74

    Article  PubMed Central  PubMed  Google Scholar 

  12. Zhang F.X., Kirschning C.J., Mancinelli R., Xu X.P., Jin Y., Faure E., et al., Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes, J. Biol. Chem., 1999, 274, 7611–7619

    Article  CAS  PubMed  Google Scholar 

  13. Bird A.C., Bressler N.M., Bressler S.B., An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group., Surv. Ophthalmol., 1995, 39, 367–374

    Article  CAS  PubMed  Google Scholar 

  14. Beatty S., Koh H., Phil M., Henson D., Boulton M., The role of oxidative stress in the pathogenesis of age-related macular degeneration, Surv. Ophthalmol., 2000, 45, 115–134

    Article  CAS  PubMed  Google Scholar 

  15. Uh A., Nicholson R.C., Gonzalez G.V., Simmons C.F., Gombart A., Smith R., et al., Lipopolysaccharide stimulation of trophoblasts induces corticotropinreleasing hormone expression through MyD88, Am. J. Obstet. Gynecol., 2008, 199, 317.e1–6.

    Google Scholar 

  16. Uh A., Simmons C.F., Bresee C., Khoury N., Gombart A.F., Nicholson R.C., et al., MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone(CRH) expression in JEG3 choriocarcinoma cell line, Reprod. Biol. Endocrinol., 2009, 7, 74

    Article  PubMed Central  PubMed  Google Scholar 

  17. Kumar M.V., Nagineni C.N., Chin M.S., Hooks J.J., Detrick B., Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells, J. Neuroimmunol., 2004, 153, 7–15

    Article  CAS  PubMed  Google Scholar 

  18. Yu F.S., Hazlett L.D., Toll-like Receptors and the Eye, Invest. Ophthalmol. Vis. Sci., 2006, 47, 1255–1263

    Article  PubMed Central  PubMed  Google Scholar 

  19. Martin P.M., Ananth S., Cresci G., Roon P., Smith S., Ganapathy V., Expression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium, Mol. Vis., 2009, 15, 362–372

    CAS  PubMed  Google Scholar 

  20. Miller K., Wang M., Gralow J., Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer, N. Engl. J. Med., 2007, 357, 2666–2676

    Article  CAS  PubMed  Google Scholar 

  21. Brechner R.J., Rosenfeld P.J., Babish J.D., Caplan S., Pharmacotherapy for neovascular age-related macular degeneration: an analysis of the 100% 2008 Medicare feefor- service Part B claims file, Am. J. Ophthalmol., 2011, 151, 887–895

    Article  PubMed  Google Scholar 

  22. Kook D., Wolf A., Kreutzer T., Neubauer A., Strauss R., Ulbig M., et al., Long-term effect of intravitreal bevacizumab(Avastin) in patients with chronic diffuse diabetic macular edema, Retina, 2008, 28, 1053–1060

    Article  PubMed  Google Scholar 

  23. Waintraub S.E., Tuchman V., The role of maintenance bevacizumab in patients with metastatic breast cancer treated with chemotherapy and bevacizumab upon achieving complete response or maximal radiologic response with stable disease, J. Clin. Oncol., 2008, 26(20 suppl), 120–122

    Google Scholar 

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Authors and Affiliations

  1. Henan Eye Institute, Henan Eye Hospital, Zhengzhou, 450003, China

    Zhi Li Wang, Shi Qing Li, Li Ya Wang & Ying Li Dong

  2. The Second People’s Hospital of Zhengzhou, Zhengzhou, 450006, China

    Bao di Qiao

  3. The Eye Hospital of Wenzhou Medical University, Wenzhou, China

    Guo Xing Li

Authors
  1. Zhi Li Wang
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  2. Bao di Qiao
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  3. Guo Xing Li
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  4. Shi Qing Li
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  5. Li Ya Wang
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  6. Ying Li Dong
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Corresponding author

Correspondence to Ying Li Dong.

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These authors contributed equally to this work.

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Wang, Z.L., di Qiao, B., Li, G.X. et al. Bevacizumab cured age-related macular degeneration (AMD) via down-regulate TLR2 pathway. cent.eur.j.biol. 9, 469–475 (2014). https://doi.org/10.2478/s11535-014-0290-5

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  • DOI: https://doi.org/10.2478/s11535-014-0290-5

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