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

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....

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Autores principales: Rodgers, Cooper D, Lukowski, Zachary L, Min, Jeff, Martorana, Gina M, Wilson, Mary-Kate, Schaefer, Jamie L, Levine, Monica A, Meyers, Craig A, Blake, C Richard, Schultz, Gregory S, Sherwood, Mark B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Jaypee Brothers Medical Publishers 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710929/
https://www.ncbi.nlm.nih.gov/pubmed/31496560
http://dx.doi.org/10.5005/jp-journals-10078-1246
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author Rodgers, Cooper D
Lukowski, Zachary L
Min, Jeff
Martorana, Gina M
Wilson, Mary-Kate
Schaefer, Jamie L
Levine, Monica A
Meyers, Craig A
Blake, C Richard
Schultz, Gregory S
Sherwood, Mark B
author_facet Rodgers, Cooper D
Lukowski, Zachary L
Min, Jeff
Martorana, Gina M
Wilson, Mary-Kate
Schaefer, Jamie L
Levine, Monica A
Meyers, Craig A
Blake, C Richard
Schultz, Gregory S
Sherwood, Mark B
author_sort Rodgers, Cooper D
collection PubMed
description 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. HOW TO CITE THIS ARTICLE: Rodgers CD, Lukowski ZL, et al. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37–41.
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spelling pubmed-67109292019-09-06 Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid Rodgers, Cooper D Lukowski, Zachary L Min, Jeff Martorana, Gina M Wilson, Mary-Kate Schaefer, Jamie L Levine, Monica A Meyers, Craig A Blake, C Richard Schultz, Gregory S Sherwood, Mark B J Curr Glaucoma Pract Research Article 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. HOW TO CITE THIS ARTICLE: Rodgers CD, Lukowski ZL, et al. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37–41. Jaypee Brothers Medical Publishers 2019 /pmc/articles/PMC6710929/ /pubmed/31496560 http://dx.doi.org/10.5005/jp-journals-10078-1246 Text en Copyright © 2019; Jaypee Brothers Medical Publishers (P) Ltd. This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Article
Rodgers, Cooper D
Lukowski, Zachary L
Min, Jeff
Martorana, Gina M
Wilson, Mary-Kate
Schaefer, Jamie L
Levine, Monica A
Meyers, Craig A
Blake, C Richard
Schultz, Gregory S
Sherwood, Mark B
Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid
title Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid
title_full Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid
title_fullStr Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid
title_full_unstemmed Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid
title_short Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid
title_sort modulating ocular scarring in glaucoma filtration surgery using the epigenetic adjunct suberoylanilide hydroxamic acid
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710929/
https://www.ncbi.nlm.nih.gov/pubmed/31496560
http://dx.doi.org/10.5005/jp-journals-10078-1246
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