Skip to main content
NCBI home page
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 1998 Jul;82(7):816–820. doi: 10.1136/bjo.82.7.816

Suramin inhibits wound healing following filtering procedures for glaucoma

H Mietz 1, P Chevez-Barrios 1, R Feldman 1, M Lieberman 1
PMCID: PMC1722692  PMID: 9924379

Abstract

BACKGROUND—Trabeculectomies are the most frequently performed procedures in surgically treating eyes with glaucoma. Failures are caused by fibrosis in the external ostium of the filtering procedure. In order to inhibit the fibrotic wound healing reaction, a new pharmacological approach using suramin, which inhibits a variety of important growth factors was used.
METHODS—Pigmented rabbits were used and filtering procedures performed. Suramin was applied with concentrations ranging from 10 mg/ml to 333 mg/ml once during surgery and four times following surgery. The success of the filtering procedure was assessed by intraocular pressure measurements. To evaluate possible intraocular toxic effects, treated eyes were histopathologically evaluated after 4 weeks, and the ciliary body adjacent to the site of application was examined using electron microscopy.
RESULTS—With concentrations of suramin of 200 mg/ml and 333 mg/ml, the trabeculectomies were patent longer than in the controls and in eyes operated with mitomycin C, which currently is the most frequently used antiproliferative drug to enhance the outcome of surgery in humans. No severe toxic effects to the ciliary epithelium were seen in suramin treated eyes.
CONCLUSIONS—This study demonstrates for the first time the efficiency of a substance that broadly inhibits the action of growth factors on target cells in the setting of ocular wound healing. In this in vivo model, suramin has been shown to be highly effective in preventing scarring and in having fewer toxic side effects than usually used antimetabolites. These results therefore may suggest a new approach to the surgical treatment of glaucoma.

 Keywords: glaucoma; wound healing; suramin; trabeculectomy; rabbits

Full Text

The Full Text of this article is available as a PDF (147.5 KB).

Figure 1  .

Figure 1  

Open in a new tab

Electron micrograph of characteristic portions of the ciliary body epithelium of rabbit eyes 4 weeks following filtering surgery. (A) Control operated with PBS. No abnormalities are present. (B) MMC treated eye. There is condensation of cytoplasm, irregularities of the endoplasmic reticulum, and large intra- and intercellular vacuoles. (C) (D) Eyes treated with suramin at a concentration of 333 mg/ml. The structures of the cells appear intact with only small intercellular vacuoles present. The cell organelles (D) are not pathologically altered. (A, B, C: original magnification, × 2600; D: original magnification, × 5000).    

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Araujo S. V., Spaeth G. L., Roth S. M., Starita R. J. A ten-year follow-up on a prospective, randomized trial of postoperative corticosteroids after trabeculectomy. Ophthalmology. 1995 Dec;102(12):1753–1759. doi: 10.1016/s0161-6420(95)30797-x. [DOI] [PubMed] [Google Scholar]
  2. Border W. A., Noble N. A. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994 Nov 10;331(19):1286–1292. doi: 10.1056/NEJM199411103311907. [DOI] [PubMed] [Google Scholar]
  3. Cairns J. E. Trabeculectomy. Preliminary report of a new method. Am J Ophthalmol. 1968 Oct;66(4):673–679. [PubMed] [Google Scholar]
  4. Campochiaro P. A., Hackett S. F., Vinores S. A., Freund J., Csaky C., LaRochelle W., Henderer J., Johnson M., Rodriguez I. R., Friedman Z. Platelet-derived growth factor is an autocrine growth stimulator in retinal pigmented epithelial cells. J Cell Sci. 1994 Sep;107(Pt 9):2459–2469. doi: 10.1242/jcs.107.9.2459. [DOI] [PubMed] [Google Scholar]
  5. Chamberlain J., Shah M., Ferguson M. W. The effect of suramin on healing adult rodent dermal wounds. J Anat. 1995 Feb;186(Pt 1):87–96. [PMC free article] [PubMed] [Google Scholar]
  6. Desjardins D. C., Parrish R. K., 2nd, Folberg R., Nevarez J., Heuer D. K., Gressel M. G. Wound healing after filtering surgery in owl monkeys. Arch Ophthalmol. 1986 Dec;104(12):1835–1839. doi: 10.1001/archopht.1986.01050240109050. [DOI] [PubMed] [Google Scholar]
  7. Deuel T. F., Kawahara R. S., Mustoe T. A., Pierce A. F. Growth factors and wound healing: platelet-derived growth factor as a model cytokine. Annu Rev Med. 1991;42:567–584. doi: 10.1146/annurev.me.42.020191.003031. [DOI] [PubMed] [Google Scholar]
  8. Doxey D. L., Ng M. C., Dill R. E., Iacopino A. M. Platelet-derived growth factor levels in wounds of diabetic rats. Life Sci. 1995;57(11):1111–1123. doi: 10.1016/0024-3205(95)02056-o. [DOI] [PubMed] [Google Scholar]
  9. Hayreh S. S. The 1994 Von Sallman Lecture. The optic nerve head circulation in health and disease. Exp Eye Res. 1995 Sep;61(3):259–272. doi: 10.1016/s0014-4835(05)80121-6. [DOI] [PubMed] [Google Scholar]
  10. Hitchings R. A., Grierson I. Clinico pathological correlation in eyes with failed fistulizing surgery. Trans Ophthalmol Soc U K. 1983;103(Pt 1):84–88. [PubMed] [Google Scholar]
  11. Jampel H. D., McGuigan L. J., Dunkelberger G. R., L'Hernault N. L., Quigley H. A. Cellular proliferation after experimental glaucoma filtration surgery. Arch Ophthalmol. 1988 Jan;106(1):89–94. doi: 10.1001/archopht.1988.01060130095036. [DOI] [PubMed] [Google Scholar]
  12. Khaw P. T., Occleston N. L., Schultz G., Grierson I., Sherwood M. B., Larkin G. Activation and suppression of fibroblast function. Eye (Lond) 1994;8(Pt 2):188–195. doi: 10.1038/eye.1994.44. [DOI] [PubMed] [Google Scholar]
  13. Levine J. H., Moses H. L., Gold L. I., Nanney L. B. Spatial and temporal patterns of immunoreactive transforming growth factor beta 1, beta 2, and beta 3 during excisional wound repair. Am J Pathol. 1993 Aug;143(2):368–380. [PMC free article] [PubMed] [Google Scholar]
  14. Lin R. Y., Sullivan K. M., Argenta P. A., Meuli M., Lorenz H. P., Adzick N. S. Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair. Ann Surg. 1995 Aug;222(2):146–154. doi: 10.1097/00000658-199508000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miller M. H., Grierson I., Unger W. I., Hitchings R. A. Wound healing in an animal model of glaucoma fistulizing surgery in the rabbit. Ophthalmic Surg. 1989 May;20(5):350–357. [PubMed] [Google Scholar]
  16. Murali S., Hardten D. R., DeMartelaere S., Olevsky O. M., Mindrup E. A., Hecht M. L., Karlstad R., Chan C. C., Holland E. J. Effect of topically administered platelet-derived growth factor on corneal wound strength. Curr Eye Res. 1994 Dec;13(12):857–862. doi: 10.3109/02713689409015086. [DOI] [PubMed] [Google Scholar]
  17. Nouri-Mahdavi K., Brigatti L., Weitzman M., Caprioli J. Outcomes of trabeculectomy for primary open-angle glaucoma. Ophthalmology. 1995 Dec;102(12):1760–1769. doi: 10.1016/s0161-6420(95)30796-8. [DOI] [PubMed] [Google Scholar]
  18. Palmer S. S. Mitomycin as adjunct chemotherapy with trabeculectomy. Ophthalmology. 1991 Mar;98(3):317–321. doi: 10.1016/s0161-6420(91)32293-0. [DOI] [PubMed] [Google Scholar]
  19. Pejnović N., Lilić D., Zunić G., Colić M., Kataranovski M., Dujić A. Aberrant levels of cytokines within the healing wound after burn injury. Arch Surg. 1995 Sep;130(9):999–1006. doi: 10.1001/archsurg.1995.01430090085025. [DOI] [PubMed] [Google Scholar]
  20. Pierce G. F., Tarpley J. E., Tseng J., Bready J., Chang D., Kenney W. C., Rudolph R., Robson M. C., Vande Berg J., Reid P. Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds. J Clin Invest. 1995 Sep;96(3):1336–1350. doi: 10.1172/JCI118169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Quigley H. A., Addicks E. M., Green W. R. Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol. 1982 Jan;100(1):135–146. doi: 10.1001/archopht.1982.01030030137016. [DOI] [PubMed] [Google Scholar]
  22. Rich A. M., McPherson S. D. Trabeculectomy in the owl monkey. Ann Ophthalmol. 1973 Oct;5(10):1082–1088. [PubMed] [Google Scholar]
  23. Seetner A., Morin J. D. Healing of trabeculectomies in rabbits. Can J Ophthalmol. 1979 Apr;14(2):121–125. [PubMed] [Google Scholar]
  24. Shah M., Foreman D. M., Ferguson M. W. Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta. Lancet. 1992 Jan 25;339(8787):213–214. doi: 10.1016/0140-6736(92)90009-r. [DOI] [PubMed] [Google Scholar]
  25. Stein C. A. Suramin: a novel antineoplastic agent with multiple potential mechanisms of action. Cancer Res. 1993 May 15;53(10 Suppl):2239–2248. [PubMed] [Google Scholar]
  26. Sullivan K. M., Lorenz H. P., Meuli M., Lin R. Y., Adzick N. S. A model of scarless human fetal wound repair is deficient in transforming growth factor beta. J Pediatr Surg. 1995 Feb;30(2):198–203. doi: 10.1016/0022-3468(95)90560-x. [DOI] [PubMed] [Google Scholar]
  27. TENG C. C., CHI H. H., KATZIN H. M. Histology and mechanism of filtering operations. Am J Ophthalmol. 1959 Jan;47(1 Pt 1):16–33. doi: 10.1016/s0002-9394(14)78135-8. [DOI] [PubMed] [Google Scholar]
  28. Thomas D. W., O'Neill I. D., Harding K. G., Shepherd J. P. Cutaneous wound healing: a current perspective. J Oral Maxillofac Surg. 1995 Apr;53(4):442–447. doi: 10.1016/0278-2391(95)90721-1. [DOI] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES