使用表观遗传辅助药物辛二酰苯胺异羟肟酸调节青光眼滤过手术中的眼部瘢痕形成

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

作者信息

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

机构信息

Department of Ophthalmology, University of Florida, Gainesville, Florida, USA; Department of Ophthalmology, University of Kansas School of Medicine, Kansas City, Kansas, USA.

Department of Ophthalmology, University of Florida, Gainesville, Florida, USA; Department of Ophthalmology, Medical College of Georgia-Augusta University, Augusta, Georgia, USA.

出版信息

J Curr Glaucoma Pract. 2019 Jan-Apr;13(1):37-41. doi: 10.5005/jp-journals-10078-1246.

DOI:10.5005/jp-journals-10078-1246

PMID:31496560

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6710929/

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 ( = 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 ( = 0.01) and the experimental group treated with the SAHA ( = 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, Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37-41.

摘要

目的

本研究旨在评估一种具有广泛表观遗传活性的组蛋白去乙酰化酶抑制剂（HDI）——辛二酰苯胺异羟肟酸（SAHA）作为兔模型青光眼滤过手术（GFS）辅助治疗手段在提高滤过泡存活率方面的有效性。

材料与方法

18只新西兰白兔左眼接受GFS，并随机分为三组，分别在手术结束时结膜下（SC）注射0.1 mL SAHA（9.25 μg/mL）或平衡盐溶液（BSS），或术中局部应用0.4 mg/mL丝裂霉素C（MMC）3分钟。比较滤过泡存活率和组织学情况。

结果

接受SAHA注射的兔滤过泡平均（均值±标准差）存活23.2±2.7天。根据单因素方差分析（ANOVA），接受SAHA注射的兔与接受BSS注射的兔相比，滤过泡存活率虽有改善但无统计学意义，接受BSS注射的兔平均存活时间为19.7±2.7天（P = 0.38）。术中局部应用MMC的眼平均存活32.5±3.3天，显著长于接受BSS治疗的对照组（P = 0.01）和接受SAHA治疗的实验组（P = 0.0495）。SAHA耐受性良好，未出现明显的无血管化、坏死或结膜变薄。