Skip to main content
SpringerLink
Log in

Effects of mitomycin C on the expression of proliferating cell nuclear antigen after filtering surgery in rabbits

  • Laboratory Investigation
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

• Background: The aim of the study was to evaluate the effects of mitomycin C on the cell replication activity in wound healing following experimental filtration surgery. • Methods: Trabeculectomy with or without application of mitomycin C was performed on albino rabbit eyes. At 1, 4, 7, 14, and 28 days after surgery, the expression of proliferating cell nuclear antigen, a marker of cell proliferation, in the filtering site was examined immunohistochemically using a streptavidin-biotin complex method. • Results: In control eyes that underwent trabeculectomy but did not receive mitomycin C, the number of immunoreactive cells increased 4–7 days after operation and decreased markedly at around 14 days. The filtering site was obstructed histologically at 4–7 days after operation. In the mitomycin C-treated eyes, immunoreactive cells appeared 4 days after surgery but disappeared by 7 days at the surgical site. The number of immunoreactive cells in the treated eyes was much lower than that in control eyes. • Conclusion: The cell replication activity was markedly inhibited by administration of mitomycin C. The filtering site remained open for 28 days after surgery, whereas it was completely obstructed within 7 days in control eyes. Immunocytochemistry for proliferating cell nuclear antigen, as used in this study, is a simple and reliable method for detection of cell replication activity.

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. Bergstrom TL, Wilkinson WS, Skuta GL, Watnick RL, Elner VM (1991) The effect of subconjunctival mitomycin C on glaucoma filtration surgery in rabbits. Arch Ophthalmol 109:1725–1730

    Google Scholar 

  2. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 326:515–517

    Google Scholar 

  3. Celis JE, Bravo R, Larsen PM, Fey SJ (1984) Cyclin: a nuclear protein whose level correlates directly with the proliferative state of normal as well as transformed cells. Leuk Res 8: 143–157

    Google Scholar 

  4. Charles JB, Ganthier R Jr, Wilson MR, Lee DA, Baker RS, Leong KW, Glasgow BJ (1991) Use of biopolymers impregnated with mitomycin in glaucoma filtration surgery in rabbits. Ophthalmology 98:503–508

    Google Scholar 

  5. Chen CW, Huang HT, Shen MM (1986) Enhancement of intraocular pressure control effect of trabeculectomy by local application of anticancer drugs. Acta XXV Concil Ophthalmol 2:1487–1491

    Google Scholar 

  6. Chen CW, Huang HT, Bair JS, Lee CC (1990) Trabeculectomy with simultaneous topical application of mitomycin C in refractory glaucoma. J Ocul Pharmacol 6: 175–182

    Google Scholar 

  7. Desjardins DC, Parrish RK II, Folberg R, Nevarez J, Heuer DK, Gressel MG (1986) Wound healing after filtering surgery in owl monkeys. Arch Ophthalmol 104:1835–1839

    Google Scholar 

  8. Fukuchi T, Sawaguchi S, Hara H, Shirakashi M, Iwata K (1992) Extracellular matrix changes of the optic nerve lamina cribrosa in monkey eyes with experimentally chronic glaucoma. Graefes Arch Clin Exp Ophthalmol 230:421–427

    Google Scholar 

  9. Hall PA, Levison DA, Woods AL, Yu CC-W, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R, Weseem NH, Lane DP (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162: 285–294

    Google Scholar 

  10. Hata T, Sano Y, Sugawara R, Matsumae A, Kanamori K, Shima T, Hoshi T (1956) Mitomycin, a new antibiotic from streptomyces. J Antibiotics Ser 9: 141–146

    Google Scholar 

  11. Hayasaka S, Noda S, Yamamoto Y, Setogawa T (1988) Postoperative instillation of low-dose mitomycin C in the treatment of primary pterygium. Am J Ophthalmol 106:715–718

    Google Scholar 

  12. He W, Meyer JS, Scrivner DL, Koehm S, Hughs J (1994) Assessment of proliferating cell nuclear antigen (PCNA) in breast cancer using anti-PCNA PC10 and 19A2: correlation with 5bromo-2-deoxyuridine or tritiated thymidine labeling and flow cytometric analysis. Biotechnic Histochem 69:203–212

    Google Scholar 

  13. Jampel HD (1992) Effects of brief exposure to mitomycin C on viability and proliferation of cultured human Tenon's capsule fibroblasts. Ophthalmology 99:1471–1476

    Google Scholar 

  14. Jampel HD, MaGuigan LJB, Dunkelberger GR, L'Hernault NL, Quigley HA (1988) Cellular proliferation after experimental glaucoma filtration surgery. Arch Ophthalmol 106: 89–94

    Google Scholar 

  15. Kitazawa Y, Kawase K, Matsushita H, Minobe M (1991) Trabeculectomy with mitomycin: a comparative study with fluorouracil. Arch Ophthalmol 109:1693–1698

    Google Scholar 

  16. Liang LL, Epstein DL (1992) Comparison of mitomycin C and 5-fluorouracil on filtration surgery success in rabbit eyes. J Glaucoma 1: 87–93

    Google Scholar 

  17. Mathews MB, Bernstein RM, Franza BR, Garrels JI (1984) Identity of the proliferating cell nuclear antigen and cyclin. Nature 308: 374–376

    Google Scholar 

  18. Megevand GS, Salmon JF, Scholtz RP, Murray AND (1995) The effect of reducing the exposure time of mitomycin C in glaucoma filtering surgery. Ophthalmology 102:84–90

    Google Scholar 

  19. Mietz H, Brunner R, Addicks K, Krieglstein GK (1993) Histopathology of an avascular filtering bleb after trabeculectomy with mitomycin C. J Glaucoma 2:266–270

    Google Scholar 

  20. Miller MH, Grierson I, Unger WI, Hitchings RA (1989) Wound healing in an animal model for glaucoma fistulizing surgery in the rabbit. Ophthalmic Surg 20: 350–357

    Google Scholar 

  21. Nagahori M, Niki S, Kigasawa K (1994) A case of scleromalacia with fundus involvement following instillation of mitomycin C. Jap Rev Clin Ophthalmol 88:162–164

    Google Scholar 

  22. Nguyen KD, Reyes MR, Lee DA (1995) Control of wound healing following glaucoma surgery. J Claucoma 4:130–135

    Google Scholar 

  23. Palmer SS (1991) Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology 98: 317–321

    Google Scholar 

  24. Prelich G, Tan C-K, Kostura M, Mathews MB, So AG, Downey KM, Stillman B (1987) Functional identity of proliferating cell nuclear antigen and a DNA- polymerase-delta auxiliary protein. Nature 326:517–520

    Google Scholar 

  25. Rubinfeld RS, Pfister RR, Stein RM, Foster CS, Martin NF, Stoleru S, Talley AR, Speaker MG (1992) Serious complications of topical mitomycin C after pterygium surgery. Ophthalmology 99:1647–1654

    Google Scholar 

  26. Seetner A, Morin JD (1979) Healing of the trabeculectomies in rabbits. Can J Ophthalmol 14:121–125

    Google Scholar 

  27. Skuta GL, Parrish RK II (1987) Wound healing in glaucoma surgery. Surv Ophthalmol 32:149–170

    Google Scholar 

  28. Skuta GL, Beeson CC, Higginbotham EJ, Lichter PR, Musch DC, Bergstrom TJ, Klein TB, Falck FY (1992) Intraoperative mitomycin versus postoperative 5-fluorouracil in high-risk glaucoma filtering surgery. Ophthalmology 99:438–444

    Google Scholar 

  29. Takasaki Y, Deng J-S, Tan EM (1981) A nuclear antigen associated with cell proliferation and blast transformation. J Exp Med 154:1899–1909

    Google Scholar 

  30. Tehery MM, Lee DA (1989) Pharmacologic control of wound healing in glaucoma filtration surgery. J Ocul Pharmacol 5:155–179

    Google Scholar 

  31. Tomasz M, Lipman R, Chowdary D, Pawlak J, Verdine GL, Nakaishi K (1987) Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA. Science 235:1204–1208

    Google Scholar 

  32. Waseem NH, Lane DP (1990) Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA): structural conservation and the detection of a nucleolar form. J Cell Sci 96:121–129

    Google Scholar 

  33. Watanabe J (1993) Effects of mitomycin C on wound healing following trabeculectomy in rabbits. Folia Ophthalmol Jpn 44: 839–845

    Google Scholar 

  34. Yamamoto T, Varani J, Soong HK, Litchter PR (1990) Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts. Ophthalmology 97:1204–1210

    Google Scholar 

  35. Yamanouchi U, Mishima K (1967) Eye lesions due to mitomycin C instillation after pterygium operation. Folia Ophthalmol Jap 18: 854–861

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Niigata University, School of Medicine, Niigata, Japan

    Joji Watanabe, Shoichi Sawaguchi, Takeo Fukuchi & Haruki Abe

  2. Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, 1855 West Taylor Street, 60612, Chicago, IL, USA

    LiLi Zhou

Authors
  1. Joji Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shoichi Sawaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takeo Fukuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haruki Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. LiLi Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Watanabe, J., Sawaguchi, S., Fukuchi, T. et al. Effects of mitomycin C on the expression of proliferating cell nuclear antigen after filtering surgery in rabbits. Graefe's Arch Clin Exp Ophthalmol 235, 234–240 (1997). https://doi.org/10.1007/BF00941765

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00941765

Keywords

Search

Navigation