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VOLUME 13 , ISSUE 1 ( January-April, 2019 ) > List of Articles

RESEARCH ARTICLE

Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid

Cooper D Rodgers, Zachary L Lukowski, Jeff Min, Gina M Martorana, Mary-Kate Wilson, Jamie L Schaefer, Monica A Levine, Craig A Meyers, C Richard Blake, Gregory S Schultz, Mark B Sherwood

Keywords : Epigenetics, Glaucoma, Glaucoma filtration surgery, SAHA, Suberoylanilide hydroxamic acid, Trabeculectomy, Vorinostat

Citation Information : Rodgers CD, Lukowski ZL, Min J, Martorana GM, Wilson M, Schaefer JL, Levine MA, Meyers CA, Blake CR, Schultz GS, Sherwood MB. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019; 13 (1):37-41.

DOI: 10.5005/jp-journals-10078-1246

License: CC BY-NC 4.0

Published Online: 01-09-2019

Copyright Statement:  Copyright © 2019; The Author(s).


Abstract

Aim: The aim of this study is to assess the effectiveness of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDI) with a broad spectrum epigenetic activity, in improving filtration bleb survival as an adjunct therapy to glaucoma filtration surgery (GFS) in the rabbit model. Materials and methods: Eighteen New Zealand White rabbits underwent GFS in the left eye and were randomized to receive either a subconjunctival (SC) injection of 0.1 mL SAHA (9.25 μg/mL) or balanced saline solution (BSS) at the end of surgery, or a 3-minute intraoperative topical application of 0.4 mg/mL mitomycin-C (MMC). Bleb survival and histology were compared. Results: Blebs of rabbits receiving injections of SAHA survived an average (mean ± SD) of 23.2 ± 2.7 days. SAHA rabbits showed a nonsignificant improvement over rabbits that received an injection of BSS, which had a mean survival time of 19.7 ± 2.7 days (p = 0.38) according to a one-way analysis of variance (ANOVA). Eyes receiving intraoperative topical MMC survived an average of 32.5 ± 3.3 days, which is significantly longer than both the control group treated with BSS (p = 0.01) and the experimental group treated with the SAHA (p = 0.0495). SAHA was well tolerated and showed no significant avascularity, necrosis, or conjunctival thinning. Conclusion: Although it was well tolerated, a single intraoperative injection of SAHA did not significantly prolong bleb survival in the rabbit model. Clinical significance: Epigenetic adjuncts hold promise for improving GFS outcome; however, future studies must continue to examine different administration protocols and dosages to substantiate their efficacy.

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  1. Burr J, Azuara-Blanco A, et al. Medical vs surgical interventions for open angle glaucoma. Cochrane Database Syst Rev 2012;(9):CD004399. DOI: 10.1002/14651858.CD004399.pub3.
  2. DeBry PW, Perkins TW, et al. Incidence of late-onset bleb-related complications following trabeculectomy with mitomycin. Arch Ophthalmol 2002;120(3):297–300. DOI: 10.1001/archopht.120.3.297.
  3. Francis BA, Du LT, et al. Histopathologic features of conjunctival filtering blebs. Arch Ophthalmol 2005;123(2):166–170. DOI: 10.1001/archopht.123.2.166.
  4. Muckley ED, Lehrer RA. Late-onset blebitis/endophthalmitis: incidence and outcomes with mitomycin C. Optom Vis Sci 2004;81(7):499–504. DOI: 10.1097/00006324-200407000-00010.
  5. Martorana GM, Schaefer JL, et al. Sequential Therapy with Saratin, Bevacizumab and Ilomastat to Prolong Bleb Function following Glaucoma Filtration Surgery in a Rabbit Model. PLoS One 2015;10(9):e0138054. DOI: 10.1371/journal.pone.0138054.
  6. Anand N, Arora S, et al. Mitomycin C augmented glaucoma surgery: evolution of filtering bleb avascularity, transconjunctival oozing, and leaks. Br J Ophthalmol 2006;90(2):175–180. DOI: 10.1136/bjo.2005.077800.
  7. Beckers HJ, Kinders KC, et al. Five-year results of trabeculectomy with mitomycin C. Graefes Arch Clin Exp Ophthalmol 2003;241(2):106.110. DOI: 10.1007/s00417-002-0621-5.
  8. Bindlish R, Condon GP, et al. Efficacy and safety of mitomycin-C in primary trabeculectomy: five-year follow-up. Ophthalmology 2002;109(7):1336.1341. DOI: 10.1016/S0161-6420(02)01069-2, discussion 1341.1332.
  9. Li Z, Van Bergen T, et al. Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery. Invest Ophthalmol Vis Sci 2009;50(11):5217.5225. DOI: 10.1167/iovs.08-2662.
  10. Goldberg AD, Allis CD, et al. Epigenetics: a landscape takes shape. Cell 2007;128(4):635.638. DOI: 10.1016/j.cell.2007.02.006.
  11. Kouzarides T. Chromatin modifications and their function. Cell 2007;128(4):693.705. DOI: 10.1016/j.cell.2007.02.005.
  12. Heerboth S, Lapinska K, et al. Use of epigenetic drugs in disease: an overview. Genet Epigenet 2014;6:9.19. DOI: 10.4137/GEG.S12270.
  13. He S, Li X, et al. Review: epigenetic mechanisms in ocular disease. Mol Vis 2013;19:665.674.
  14. Biermann J, Grieshaber P, et al. Valproic acid-mediated neuroprotection and regeneration in injured retinal ganglion cells. Invest Ophthalmol Vis Sci 2010;51(1):526.534. DOI: 10.1167/iovs.09-3903.
  15. Gauthier AC, Liu J. Epigenetics and Signaling Pathways in Glaucoma. Biomed Res Int 2017;2017:5712341. DOI: 10.1155/2017/5712341.
  16. Kavanaugh SM, White LA, et al. Vorinostat: a novel therapy for the treatment of cutaneous T-cell lymphoma. Am J Health Syst Pharm 2010;67(10):793.797. DOI: 10.2146/ajhp090247.
  17. Deroanne CF, Bonjean K, et al. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 2002;21(3):427.436. DOI: 10.1038/sj.onc.1205108.
  18. Sanders YY, Hagood JS, et al. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur Respir J 2014;43(5):1448.1458. DOI: 10.1183/09031936.00095113.
  19. Sharma A, Sinha NR, et al. Role of 5′ŒTG3′Œ-interacting factors (TGIFs) in Vorinostat (HDAC inhibitor)-mediated Corneal Fibrosis Inhibition. Mol Vis 2015;21:974.984.
  20. Komorowsky C, Ocker M, et al. Differential regulation of connective tissue growth factor in renal cells by histone deacetylase inhibitors. J Cell Mol Med 2009;13(8B):2353.2364. DOI: 10.1111/j.1582- 4934.2008.00674.x.
  21. Tandon A, Tovey JC, et al. Vorinostat: a potent agent to prevent and treat laser-induced corneal haze. J Refract Surg 2012;28(4):285.290. DOI: 10.3928/1081597X-20120210-01.
  22. Li X, Zhou Q, et al. Inhibition of multiple pathogenic pathways by histone deacetylase inhibitor SAHA in a corneal alkali-burn injury model. Mol Pharm 2013;10(1):307.318. DOI: 10.1021/mp300445a.
  23. Min J, Lukowski ZL, et al. Comparison of single vs multiple injections of the protein saratin for prolonging bleb survival in a rabbit model. Invest Ophthalmol Vis Sci 2012;53(12):7625.7630. DOI: 10.1167/iovs. 12-10120.
  24. Min J, Lukowski ZL, et al. Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model. PLoS One 2012;7(4):e35627. DOI: 10.1371/journal.pone.0035627.
  25. Rodgers CD, Meyer AM, et al. The impact of conjunctival flap method and drainage cannula diameter on bleb survival in the rabbit model. PLoS One 2018;13(5):e0196968. DOI: 10.1371/journal.pone.0196968.
  26. Fuchshofer R, Tamm ER. The role of TGF-beta in the pathogenesis of primary open-angle glaucoma. Cell Tissue Res 2012;347(1):279.290. DOI: 10.1007/s00441-011-1274-7.
  27. Bermudez JY, Webber HC, et al. HDAC Inhibitor-Mediated Epigenetic Regulation of Glaucoma-Associated TGFbeta2 in the Trabecular Meshwork. Invest Ophthalmol Vis Sci 2016;57(8):3698.3707. DOI: 10.1167/iovs16-19446.
  28. Sharma A, Mehan MM, et al. Trichostatin a inhibits corneal haze in vitro and in vivo. Invest Ophthalmol Vis Sci 2009;50(6):2695.2701. DOI: 10.1167/iovs.08-2919.
  29. Kim TH, Kim SW, et al. Co-treatment of suberoylanilide hydroxamic acid and mitomycin-C induces the apoptosis of rabbit tenon's capsule fibroblast and improves the outcome of glaucoma filtration surgery. Curr Eye Res 2008;33(3):237.245. DOI: 10.1080/02713680701875281.
  30. Doyle JW, Sherwood MB, et al. Intraoperative 5-fluorouracil for filtration surgery in the rabbit. Invest Ophthalmol Vis Sci 1993;34(12):3313.3319.
  31. Wong TT, Mead AL, et al. Matrix metalloproteinase inhibition modulates postoperative scarring after experimental glaucoma filtration surgery. Invest Ophthalmol Vis Sci 2003;44(3):1097.1103. DOI: 10.1167/iovs.02-0366.
  32. Cordeiro MF, Mead A, et al. Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and improve surgical outcome. Gene Ther 2003;10(1):59.71. DOI: 10.1038/sj.gt.3301865.
  33. Sharma A, Anumanthan G, et al. Epigenetic Modification Prevents Excessive Wound Healing and Scar Formation After Glaucoma Filtration Surgery. Invest Ophthalmol Vis Sci 2016;57(7):3381.3389. DOI: 10.1167/iovs.15-18750.
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