nach oben

Inflammation

Erschienen in:

01.08.2012

Connexin43 Modulation Inhibits Scarring in a Rabbit Eye Glaucoma Trabeculectomy Model

verfasst von: Narmadai C. Deva, Jie Zhang, Colin R. Green, Helen V. Danesh-Meyer

Erschienen in: Inflammation | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

Abstract

We investigated whether one subconjunctival injection of connexin43 antisense oligodeoxynucleotides (Cx43 AsODN) modulates postoperative scarring in a rabbit model of glaucoma trabeculectomy surgery. In a randomised, controlled, masked-observer study, 39 rabbits underwent trabeculectomy surgery with insertion of a 22-gauge cannula in the right eyes and were randomly divided into three treatment groups. Each rabbit received an injection of Cx43 AsODN in Pluronic gel, balanced salt solution or Pluronic gel alone into the formed bled. The animals were euthanized at 8 and 24 h and at 5 and 21 days. Histology and immunohistochemistry results demonstrated that Cx43 AsODN decreased Cx43 upregulation at 8 and 24 h which led to less myofibroblast upregulation at days 5 and 21 and reduced scarring at day 21 compared to controls. We conclude that postoperative use of Cx43 AsODN inhibited subconjunctival scarring and fibrosis. Cx43 AsODN injection may be a safe and effective anti-scarring agent in glaucoma trabeculectomy surgery.

Quigley, H.A., and A.T. Broman. 2006. The number of people with glaucoma worldwide in 2010 and 2020. British Journal of Ophthalmology 90: 262–267.PubMedCrossRef

Watson, P.G. 1972. Surgery of the glaucomas. British Journal of Ophthalmology 56: 299–306.PubMedCrossRef

Cairns, J.E. 1968. Trabeculectomy. Preliminary report of a new method. American Journal of Ophthalmology 66: 673–679.PubMed

Skuta, G.L., and R.K. Parrish 2nd. 1987. Wound healing in glaucoma filtering surgery. Survey of Ophthalmology 32: 149–170.PubMedCrossRef

Addicks, E.M., H.A. Quigley, W.R. Green, and A.L. Robin. 1983. Histologic characteristics of filtering blebs in glaucomatous eyes. Archives of Ophthalmology 101: 795–798.PubMedCrossRef

Migdal, C., and R. Hitchings. 1983. The developing bleb: Effect of topical antiprostaglandins on the outcome of glaucoma fistulising surgery. British Journal of Ophthalmology 67: 655–660.PubMedCrossRef

Messmer, E.M., D.M. Zapp, M.J. Mackert, M. Thiel, and A. Kampik. 2006. In vivo confocal microscopy of filtering blebs after trabeculectomy. Archives of Ophthalmology 124: 1095–1103.PubMedCrossRef

Jones, E., J. Clarke, and P.T. Khaw. 2005. Recent advances in trabeculectomy technique. Current Opinion in Ophthalmology 16: 107–113.PubMedCrossRef

Khaw, P.T., M.B. Sherwood, J.W. Doyle, M.F. Smith, I. Grierson, S. McGorray, and G.S. Schultz. 1992. Intraoperative and post operative treatment with 5-fluorouracil and mitomycin-c: Long term effects in vivo on subconjunctival and scleral fibroblasts. International Ophthalmology 16: 381–385.PubMedCrossRef

10.

Khaw, P.T., J.W. Doyle, M.B. Sherwood, I. Grierson, G. Schultz, and S. McGorray. 1993. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Archives of Ophthalmology 111: 263–267.PubMedCrossRef

11.

Greenfield, D.S., J.M. Liebmann, J. Jee, and R. Ritch. 1998. Late-onset bleb leaks after glaucoma filtering surgery. Archives of Ophthalmology 116: 443–447.PubMed

12.

Higginbotham, E.J., R.K. Stevens, D.C. Musch, K.O. Karp, P.R. Lichter, T.J. Bergstrom, and G.L. Skuta. 1996. Bleb-related endophthalmitis after trabeculectomy with mitomycin C. Ophthalmology 103: 650–656.PubMed

13.

Bindlish, R., G.P. Condon, J.D. Schlosser, J. D’Antonio, K.B. Lauer, and R. Lehrer. 2002. Efficacy and safety of mitomycin-C in primary trabeculectomy: Five-year follow-up. Ophthalmology 109: 1336–1341. discussion 1341–2.PubMedCrossRef

14.

Evans, W.H., E. De Vuyst, and L. Leybaert. 2006. The gap junction cellular internet: Connexin hemichannels enter the signalling limelight. Biochemical Journal 397: 1–14.PubMedCrossRef

15.

Goodenough, D.A., J.A. Goliger, and D.L. Paul. 1996. Connexins, connexons, and intercellular communication. Annual Review of Biochemistry 65: 475–502.PubMedCrossRef

16.

Bruzzone, R., T.W. White, and D.A. Goodenough. 1996. The cellular internet: On-line with connexins. Bioessays 18: 709–718.PubMedCrossRef

17.

Kumar, N.M., and N.B. Gilula. 1996. The gap junction communication channel. Cell 84: 381–388.PubMedCrossRef

18.

Beyer, E.C., and T.H. Steinberg. 1991. Evidence that the gap junction protein connexin-43 is the ATP-induced pore of mouse macrophages. Journal of Biological Chemistry 266: 7971–7974.PubMed

19.

Oviedo-Orta, E., P. Gasque, and W.H. Evans. 2001. Immunoglobulin and cytokine expression in mixed lymphocyte cultures is reduced by disruption of gap junction intercellular communication. The FASEB Journal 15: 768–774.CrossRef

20.

Oviedo-Orta, E., T. Hoy, and W.H. Evans. 2000. Intercellular communication in the immune system: Differential expression of connexin40 and 43, and perturbation of gap junction channel functions in peripheral blood and tonsil human lymphocyte subpopulations. Immunology 99: 578–590.PubMedCrossRef

21.

Kwak, B.R., M.S. Pepper, D.B. Gros, and P. Meda. 2001. Inhibition of endothelial wound repair by dominant negative connexin inhibitors. Molecular Biology of the Cell 12: 831–845.PubMed

22.

Oviedo-Orta, E., R.J. Errington, and W.H. Evans. 2002. Gap junction intercellular communication during lymphocyte transendothelial migration. Cell Biology International 26: 253–263.PubMedCrossRef

23.

Ehrlich, H.P., G. Gabbiani, and P. Meda. 2000. Cell coupling modulates the contraction of fibroblast-populated collagen lattices. Journal of Cellular Physiology 184: 86–92.PubMedCrossRef

24.

Coutinho, P., C. Qiu, S. Frank, C.M. Wang, T. Brown, C.R. Green, and D.L. Becker. 2005. Limiting burn extension by transient inhibition of connexin43 expression at the site of injury. British Journal of Plastic Surgery 58: 658–667.PubMedCrossRef

25.

Qiu, C., P. Coutinho, S. Frank, S. Franke, L.Y. Law, P. Martin, C.R. Green, and D.L. Becker. 2003. Targeting connexin43 expression accelerates the rate of wound repair. Current Biology 13: 1697–1703.PubMedCrossRef

26.

Mori, R., K.T. Power, C.M. Wang, P. Martin, and D.L. Becker. 2006. Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration. Journal of Cell Science 119: 5193–5203.PubMedCrossRef

27.

Cronin, M., P.N. Anderson, J.E. Cook, C.R. Green, and D.L. Becker. 2008. Blocking connexin43 expression reduces inflammation and improves functional recovery after spinal cord injury. Molecular and Cellular Neuroscience 39: 152–160.PubMedCrossRef

28.

Danesh-Meyer, H.V., R. Huang, L.F.B. Nicholson, and C.R. Green. 2008. Connexin43 antisense oligodeoxynucleotide treatment down-regulates the inflammatory response in an in vitro interphase organotypic culture model of optic nerve ischaemia. Journal of Clinical Neuroscience 15: 1253–1263.PubMedCrossRef

29.

Cordeiro, M.F., P.H. Constable, R.A. Alexander, S.S. Bhattacharya, and P.T. Khaw. 1997. Effect of varying the mitomycin-C treatment area in glaucoma filtration surgery in the rabbit. Investigative Ophthalmology & Visual Science 38: 1639–1646.

30.

Green, C.R., L.Y. Law, J.S. Lin, and D.L. Becker. 2001. Spatiotemporal depletion of connexins using antisense oligonucleotides. Methods in Molecular Biology 154: 175–185.PubMed

31.

Law, L.Y., W.V. Zhang, N.S. Stott, D.L. Becker, and C.R. Green. 2006. In vitro optimization of antisense oligodeoxynucleotide design: An example using the connexin gene family. Journal of Biomolecular Techniques 17: 270–282.PubMed

32.

Ratkay-Traub, I., B. Hopp, Z. Bor, L. Dux, D.L. Becker, and T. Krenacs. 2001. Regeneration of rabbit cornea following excimer laser photorefractive keratectomy: A study on gap junctions, epithelial junctions and epidermal growth factor receptor expression in correlation with cell proliferation. Experimental Eye Research 73: 291–302.PubMedCrossRef

33.

Darby, I., O. Skalli, and G. Gabbiani. 1990. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Laboratory Investigation 63: 21–29.PubMed

34.

Coleman, R. 2011. Picrosirius red staining revisited. Acta Histochemica 113: 231–233.PubMedCrossRef

35.

Dayan, D., Y. Hiss, A. Hirshberg, J.J. Bubis, and M. Wolman. 1989. Are the polarization colors of picrosirius red-stained collagen determined only by the diameter of the fibers? Histochemistry 93: 27–29.PubMedCrossRef

36.

Bergstrom, T.J., W.S. Wilkinson, G.L. Skuta, R.L. Watnick, and V.M. Elner. 1991. The effects of subconjunctival mitomycin-C on glaucoma filtration surgery in rabbits. Archives of Ophthalmology 109: 1725–1730.PubMedCrossRef

37.

Akman, A., B. Bilezikci, C. Kucukerdonmez, B. Demirhan, and P. Aydin. 2003. Suramin modulates wound healing of rabbit conjunctiva after trabeculectomy: Comparison with mitomycin C. Current Eye Research 26: 37–43.PubMedCrossRef

38.

Wong, T.T.L., A.L. Mead, and P.T. Khaw. 2005. Prolonged antiscarring effects of ilomastat and MMC after experimental glaucoma filtration surgery. Investigative Ophthalmology & Visual Science 46: 2018–2022.CrossRef

39.

Memarzadeh, F., R. Varma, L.-T. Lin, J.G. Parikh, L. Dustin, A. Alcaraz, and D. Eliott. 2009. Postoperative Use of bevacizumab as an antifibrotic agent in glaucoma filtration surgery in the rabbit. Investigative Ophthalmology & Visual Science 50: 3233–3237.CrossRef

40.

Mead, A.L., T.T.L. Wong, M.F. Cordeiro, I.K. Anderson, and P.T. Khaw. 2003. Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Investigative Ophthalmology & Visual Science 44: 3394–3401.CrossRef

41.

Takeuchi, K., M. Nakazawa, Y. Ebina, K. Sato, T. Metoki, Y. Miyagawa, and T. Ito. 2010. Inhibitory effects of trehalose on fibroblast proliferation and implications for ocular surgery. Experimental Eye Research 91: 567–577.PubMedCrossRef

42.

Wong, T.T.L., A.L. Mead, and P.T. Khaw. 2003. Matrix metalloproteinase inhibition modulates postoperative scarring after experimental glaucoma filtration surgery. Investigative Ophthalmology & Visual Science 44: 1097–1103.CrossRef

43.

Risek, B., F.G. Klier, and N.B. Gilula. 1994. Developmental regulation and structural organization of connexins in epidermal gap junctions. Developmental Biology 164: 183–196.PubMedCrossRef

44.

Chin, K.Y. 2011. Connexins, a new target in wound treatment. Journal of Wound Care 20: 386–390.PubMed

45.

Brandner, J.M., P. Houdek, B. Husing, C. Kaiser, and I. Moll. 2004. Connexins 26, 30, and 43: Differences among spontaneous, chronic, and accelerated human wound healing. Journal of Investigative Dermatology 122: 1310–1320.PubMedCrossRef

46.

Wang, C.M., J. Lincoln, J.E. Cook, and D.L. Becker. 2007. Abnormal connexin expression underlies delayed wound healing in diabetic skin. Diabetes 56: 2809–2817.PubMedCrossRef

47.

Li, Z., T. Van Bergen, S. Van de Veire, I. Van de Vel, H. Moreau, M. Dewerchin, P.C. Maudgal, T. Zeyen, W. Spileers, L. Moons, and I. Stalmans. 2009. Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery. Investigative Ophthalmology & Visual Science 50: 5217–5225.CrossRef

48.

Cordeiro, M.F., J.A. Gay, and P.T. Khaw. 1999. Human anti-transforming growth factor-beta2 antibody: A new glaucoma anti-scarring agent. Investigative Ophthalmology & Visual Science 40: 2225–2234.

49.

Seetner, A., and J.D. Morin. 1979. Healing of trabeculectomies in rabbits. Canadian Journal of Ophthalmology 14: 121–125.PubMed

Titel: Connexin43 Modulation Inhibits Scarring in a Rabbit Eye Glaucoma Trabeculectomy Model
verfasst von: Narmadai C. Deva
Jie Zhang
Colin R. Green
Helen V. Danesh-Meyer
Publikationsdatum: 01.08.2012
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 4/2012
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-012-9439-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Connexin43 Modulation Inhibits Scarring in a Rabbit Eye Glaucoma Trabeculectomy Model

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

Vorsicht, erhöhte Blutungsgefahr nach PCI!

Wie managen Sie die schmerzhafte diabetische Polyneuropathie?

Update Innere Medizin

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2012

Anti-inflammation Effects of Sophora flavescens Nanoparticles

Rehmannia glutinosa Suppresses Inflammatory Responses Elicited by Advanced Glycation End Products

Plasma Melatonin and Urinary 6-Hydroxymelatonin Levels in Patients with Pulmonary Tuberculosis

Lipopolysaccharide-Induced Proliferation of the Vasa Vasorum in a Rabbit Model of Atherosclerosis as Evaluated by Contrast-Enhanced Ultrasound Imaging and Histology

Resveratrol Inhibits Respiratory Syncytial Virus-Induced IL-6 Production, Decreases Viral Replication, and Downregulates TRIF Expression in Airway Epithelial Cells

Inhibition of miRNA-221 Suppresses the Airway Inflammation in Asthma

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

Vorsicht, erhöhte Blutungsgefahr nach PCI!

Wie managen Sie die schmerzhafte diabetische Polyneuropathie?

Update Innere Medizin