Topical Infliximab for the Suppression of Wound Healing Following Experimental Glaucoma Filtration Surgery

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2014 May 23

PMID 24851041

Citations 6

Authors

Burak Turgut

Kenan Eren

Mehmet Mustafa Akin

Tamer Demir

Sabiha Kobat

Affiliations

Soon will be listed here.

Abstract

Background: The purpose of this work was to look into the effects of infliximab on wound healing in experimental glaucoma filtration surgery and to compare the antifibrotic effects of this agent to that of mitomycin-C (MMC).

Methods: Twenty-eight male New Zealand White rabbits were randomly assigned to four groups, each including seven rabbits: control group, sham group, MMC group, and infliximab group. The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the MMC treatment group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC was applied intraoperatively to the scleral surgical site for three minutes. The rabbits in the infliximab treatment group underwent trabeculectomy and one drop of 10 mg/mL infliximab was instilled four times a day for 14 days after surgery. On day 14 of the experiment, the operated and control eyes were enucleated and histologically and immunohistochemically analyzed.

Results: The mean fibroblast and mononuclear cell (MNC) numbers and the mean immunostaining intensities of transforming growth factor-β (TGF-β), fibroblast growth factor-β (FGF-β), and platelet-derived growth factor (PDGF) in the sham group were higher than those of the control group (P<0.01). The mean fibroblast and MNC numbers and the mean immunostaining intensities of TGF-β, FGF-β, and PDGF in the MMC and infliximab groups were statistically significantly lower than those of the sham group (P<0.01). The mean fibroblast and MNC numbers and the mean TGF-β, FGF-β, and PDGF immunostaining intensities of the MMC and infliximab groups were similar (P>0.05).

Conclusion: Our study suggests that topical infliximab effectively suppresses the subconjunctival wound healing response after experimental glaucoma filtration surgery, reducing the MNC and fibroblast numbers and immunostaining intensities of TGF-β, FGF-β, and PDGF.

Citing Articles

Pharmacological Approaches to Modulate the Scarring Process after Glaucoma Surgery.

Collotta D, Colletta S, Carlucci V, Fruttero C, Fea A, Collino M Pharmaceuticals (Basel). 2023; 16(6).

PMID: 37375845 PMC: 10305204. DOI: 10.3390/ph16060898.

Aqueous Humor Growth Factor Levels and Trabeculectomy Outcomes in Primary Open-Angle Glaucoma Patients: A 2-Year Prospective Study.

Qian T, Fu M, Ye L, Du J, Xu X, Zhang Z Transl Vis Sci Technol. 2022; 11(10):2.

PMID: 36180030 PMC: 9547364. DOI: 10.1167/tvst.11.10.2.

Targeting Differential Roles of Tumor Necrosis Factor Receptors as a Therapeutic Strategy for Glaucoma.

Lambuk L, Ahmad S, Sadikan M, Nordin N, Kadir R, Abdul Nasir N Front Immunol. 2022; 13:857812.

PMID: 35651608 PMC: 9149562. DOI: 10.3389/fimmu.2022.857812.

Overview of cicatricial modulators in glaucoma fistulizing surgery.

de Oliveira C, Ferreira J Int Ophthalmol. 2020; 40(10):2789-2796.

PMID: 32504309 DOI: 10.1007/s10792-020-01454-w.

Wound Healing Modulation in Glaucoma Filtration Surgery- Conventional Practices and New Perspectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II).

Fan Gaskin J, Nguyen D, Ang G, OConnor J, Crowston J J Curr Glaucoma Pract. 2016; 8(2):46-53.

PMID: 26997808 PMC: 4741169. DOI: 10.5005/jp-journals-10008-1160.

References

Seibold L, Sherwood M, Kahook M . Wound modulation after filtration surgery. Surv Ophthalmol. 2012; 57(6):530-50. DOI: 10.1016/j.survophthal.2012.01.008. View

Imanishi J, Kamiyama K, Iguchi I, Kita M, Sotozono C, Kinoshita S . Growth factors: importance in wound healing and maintenance of transparency of the cornea. Prog Retin Eye Res. 1999; 19(1):113-29. DOI: 10.1016/s1350-9462(99)00007-5. View

YODAIKEN R, Bennett D . OSHA work-practice guidelines for personnel dealing with cytotoxic (antineoplastic) drugs. Occupational Safety and Health Administration. Am J Hosp Pharm. 1986; 43(5):1193-204. View

Verrecchia F, Mauviel A . TGF-beta and TNF-alpha: antagonistic cytokines controlling type I collagen gene expression. Cell Signal. 2004; 16(8):873-80. DOI: 10.1016/j.cellsig.2004.02.007. View

Lee D, Lee T, CORTES A, Kitada S . Effects of mithramycin, mitomycin, daunorubicin, and bleomycin on human subconjunctival fibroblast attachment and proliferation. Invest Ophthalmol Vis Sci. 1990; 31(10):2136-44. View

Honma Y, Nishida K, Sotozono C, Kinoshita S . Effect of transforming growth factor-beta1 and -beta2 on in vitro rabbit corneal epithelial cell proliferation promoted by epidermal growth factor, keratinocyte growth factor, or hepatocyte growth factor. Exp Eye Res. 1997; 65(3):391-6. DOI: 10.1006/exer.1997.0338. View

di Sabatino A, Ciccocioppo R, Benazzato L, Sturniolo G, Corazza G . Infliximab downregulates basic fibroblast growth factor and vascular endothelial growth factor in Crohn's disease patients. Aliment Pharmacol Ther. 2004; 19(9):1019-24. DOI: 10.1111/j.1365-2036.2004.01927.x. View

Cairns J . Trabeculectomy. Preliminary report of a new method. Am J Ophthalmol. 1968; 66(4):673-9. View

Chen C, Huang H, Bair J, Lee C . Trabeculectomy with simultaneous topical application of mitomycin-C in refractory glaucoma. J Ocul Pharmacol. 1990; 6(3):175-82. DOI: 10.1089/jop.1990.6.175. View

10.

Betsholtz C, Karlsson L, Lindahl P . Developmental roles of platelet-derived growth factors. Bioessays. 2001; 23(6):494-507. DOI: 10.1002/bies.1069. View

11.

Regatieri C, Dreyfuss J, Melo G, Lavinsky D, Farah M, Nader H . Dual role of intravitreous infliximab in experimental choroidal neovascularization: effect on the expression of sulfated glycosaminoglycans. Invest Ophthalmol Vis Sci. 2009; 50(11):5487-94. DOI: 10.1167/iovs.08-3171. View

12.

Denk P, Hoppe J, Hoppe V, Knorr M . Effect of growth factors on the activation of human Tenon's capsule fibroblasts. Curr Eye Res. 2003; 27(1):35-44. DOI: 10.1076/ceyr.27.2.35.15456. View

13.

Jampel H, McGuigan L, Dunkelberger G, LHernault N, Quigley H . Cellular proliferation after experimental glaucoma filtration surgery. Arch Ophthalmol. 1988; 106(1):89-94. DOI: 10.1001/archopht.1988.01060130095036. View

14.

Wollin M, Abele S, Bruns H, Weyand M, Kalden J, Ensminger S . Inhibition of TNF-alpha reduces transplant arteriosclerosis in a murine aortic transplant model. Transpl Int. 2008; 22(3):342-9. DOI: 10.1111/j.1432-2277.2008.00802.x. View

15.

Fujita M, Shannon J, Morikawa O, Gauldie J, Hara N, Mason R . Overexpression of tumor necrosis factor-alpha diminishes pulmonary fibrosis induced by bleomycin or transforming growth factor-beta. Am J Respir Cell Mol Biol. 2003; 29(6):669-76. DOI: 10.1165/rcmb.2002-0046OC. View

16.

Knorr M, Volker M, Denk P, Wunderlich K, Thiel H . Proliferative response of cultured human tenon's capsule fibroblasts to platelet-derived growth factor isoforms. Graefes Arch Clin Exp Ophthalmol. 1997; 235(10):667-71. DOI: 10.1007/BF00946945. View

17.

Sullivan D, Ferris M, Nguyen H, Abboud E, Brody A . TNF-alpha induces TGF-beta1 expression in lung fibroblasts at the transcriptional level via AP-1 activation. J Cell Mol Med. 2010; 13(8B):1866-76. PMC: 2855747. DOI: 10.1111/j.1582-4934.2009.00647.x. View

18.

Occleston N, Daniels J, Tarnuzzer R, Sethi K, ALEXANDER R, Bhattacharya S . Single exposures to antiproliferatives: long-term effects on ocular fibroblast wound-healing behavior. Invest Ophthalmol Vis Sci. 1997; 38(10):1998-2007. View

19.

Saika S, Yamanaka O, Baba Y, Kawashima Y, Shirai K, Miyamoto T . Accumulation of latent transforming growth factor-beta binding protein-1 and TGF beta 1 in extracellular matrix of filtering bleb and of cultured human subconjunctival fibroblasts. Graefes Arch Clin Exp Ophthalmol. 2001; 239(3):234-41. DOI: 10.1007/s004170100275. View

20.

Wilson S, Schultz G, Chegini N, Weng J, He Y . Epidermal growth factor, transforming growth factor alpha, transforming growth factor beta, acidic fibroblast growth factor, basic fibroblast growth factor, and interleukin-1 proteins in the cornea. Exp Eye Res. 1994; 59(1):63-71. DOI: 10.1006/exer.1994.1081. View