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新型角膜交联用穿透增强剂对猪眼重组人去整合素的影响。

Effect of penetration enhancer with novel corneal cross-linking using recombinant human decoron in porcine eyes.

机构信息

Department of Ophthalmology & Visual Sciences, William H. Havener Eye Institute, 915 Olentangy River Rd, Suite 5000, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Department of Biomedical Engineering, 140 W. 19th Ave., Fontana Labs the Ohio State University, Columbus, OH, USA.

出版信息

Exp Eye Res. 2021 May;206:108542. doi: 10.1016/j.exer.2021.108542. Epub 2021 Mar 17.

DOI:10.1016/j.exer.2021.108542
PMID:33744258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8098800/
Abstract

The aim of the study was to investigate the effectiveness of exogenous recombinant human decoron and an accompanying penetration-enhancing solution in stiffening ex-vivo porcine corneas both transepithelially and after de-epithelialization. Eight porcine paired eyes were treated transepithelially: one eye with a pre-treatment solution (Pre-Tx), penetration enhancing solution (PE), and decoron while the fellow eye was treated by the same protocol but without decoron. A second group included 4 de-epithelialized pairs treated identically. The final group included 4 de-epithelialized pairs with one eye treated with Pre-Tx, PE, and decoron while the fellow eye was treated without PE. Uniaxial tensile testing was used to compare the corneal stiffness between the different treatment conditions. Residual tissue underwent immunohistochemistry analysis to evaluate the depth of penetration of decoron into the corneal stroma. There was no stiffening effect exhibited among corneas treated transepithelially with decoron compared to control (P > 0.05) and poor stromal penetration was exhibited on tissue analysis. Among de-epithelialized corneas, there was a significant stiffening effect seen in those treated with decoron at 3%, 4%, 5%, & 6% strain (P < 0.05) compared to control. Among de-epithelialized corneas there was also a significant stiffening effect seen in those treated with the PE and decoron at 4%, 5%, & 6% strain (P < 0.05) with improved stromal penetration confirmed by immunohistochemistry, versus without PE. De-epithelialization is necessary for effective stromal penetration of decoron. Depth of penetration and subsequent corneal stiffening may be improved with a penetration enhancing solution. Compared to riboflavin, decoron requires shorter treatment time and spares UV light exposure.

摘要

本研究旨在探讨外源性重组人脱冠素(decoron)及其伴随的渗透增强溶液在使离体猪角膜变硬方面的有效性,既包括经上皮途径,也包括去上皮后。8 对离体猪眼进行经上皮处理:一只眼用预处理溶液(Pre-Tx)、渗透增强溶液(PE)和 decoron 处理,而对侧眼则用相同的方案处理,但不含 decoron。第二组包括 4 对去上皮的配对眼,处理方式相同。最后一组包括 4 对去上皮的配对眼,其中一只眼用 Pre-Tx、PE 和 decoron 处理,而对侧眼则不用 PE 处理。单轴拉伸试验用于比较不同处理条件下角膜的硬度。残留组织进行免疫组织化学分析,以评估 decoron 渗透到角膜基质的深度。与对照组相比,经上皮途径用 decoron 处理的角膜没有表现出僵硬效应(P>0.05),组织分析显示渗透深度较差。在去上皮的角膜中,用 3%、4%、5%和 6%应变处理的角膜用 decoron 处理有明显的僵硬效应(P<0.05),与对照组相比。在去上皮的角膜中,用 PE 和 decoron 处理的角膜在 4%、5%和 6%应变时也有明显的僵硬效应(P<0.05),免疫组织化学证实渗透增强,而没有 PE 时则没有。去上皮化是 decoron 有效渗透到基质所必需的。渗透深度和随后的角膜变硬可能会通过渗透增强溶液得到改善。与核黄素相比,decoron 所需的治疗时间更短,且避免了紫外线照射。

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引用本文的文献

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Biomechanics of Ophthalmic Crosslinking.眼用交联的生物力学。
Transl Vis Sci Technol. 2021 Apr 29;10(5):8. doi: 10.1167/tvst.10.5.8.

本文引用的文献

1
Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture.重组 Decorin 融合蛋白可减轻小鼠腹主动脉瘤的形成和破裂。
Sci Rep. 2017 Nov 20;7(1):15857. doi: 10.1038/s41598-017-16194-8.
2
Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons.腱组织中的核心蛋白聚糖和 biglycan 对于维持胶原纤维结构、纤维重排以及成熟腱组织的力学性能是必需的。
Matrix Biol. 2017 Dec;64:81-93. doi: 10.1016/j.matbio.2017.08.004. Epub 2017 Sep 5.
3
Ex Vivo Transepithelial Collagen Cross-linking in Porcine and Human Corneas Using Human Decorin Core Protein.
使用人核心蛋白聚糖核心蛋白在猪和人角膜中进行体外跨上皮胶原交联
J Refract Surg. 2016 Jun 1;32(6):410-7. doi: 10.3928/1081597X-20160428-08.
4
Recombinant Human Decorin Inhibits TGF-b1 Induced Contraction of Collagen Lattice by Keloid Fibroblasts.重组人核心蛋白聚糖抑制瘢痕疙瘩成纤维细胞中转化生长因子-β1诱导的胶原晶格收缩。
Wounds. 2009 Feb;21(2):47-56.
5
Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial.经上皮与上皮下角膜交联治疗进行性圆锥角膜的随机对照试验
Am J Ophthalmol. 2015 May;159(5):821-8.e3. doi: 10.1016/j.ajo.2015.02.005. Epub 2015 Feb 19.
6
Safety profile of accelerated corneal cross-linking versus conventional cross-linking: a comparative study on ex vivo-cultured limbal epithelial cells.加速角膜交联与传统交联的安全性概况:对体外培养的角膜缘上皮细胞的比较研究
Br J Ophthalmol. 2015 Feb;99(2):272-80. doi: 10.1136/bjophthalmol-2014-305495. Epub 2014 Dec 8.
7
Resistance of corneal RFUVA–cross-linked collagens and small leucine-rich proteoglycans to degradation by matrix metalloproteinases.角膜 RFUVA–交联胶原蛋白和小富含亮氨酸的蛋白聚糖对基质金属蛋白酶降解的抗性。
Invest Ophthalmol Vis Sci. 2013 Feb 5;54(2):1014-25. doi: 10.1167/iovs.12-11277.
8
Long term results of a prospective randomized bilateral eye comparison trial of higher fluence, shorter duration ultraviolet A radiation, and riboflavin collagen cross linking for progressive keratoconus.一项关于高能量、短持续时间紫外线A辐射联合核黄素胶原交联治疗进行性圆锥角膜的前瞻性随机双眼对照试验的长期结果
Clin Ophthalmol. 2012;6:97-101. doi: 10.2147/OPTH.S27170. Epub 2012 Jan 11.
9
Transepithelial corneal collagen cross-linking in keratoconus.交联角膜胶原在圆锥角膜中的应用。
J Refract Surg. 2010 Dec;26(12):942-8. doi: 10.3928/1081597X-20100212-09. Epub 2010 Feb 15.
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Effect of decorin and dermatan sulfate on the mechanical properties of a neocartilage.去整合素和硫酸皮肤素对新生软骨机械性能的影响。
Connect Tissue Res. 2010 Apr;51(2):159-70. doi: 10.3109/03008200903174342.