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细胞外基质蛋白在晚期圆锥角膜和正常人角膜中的表达。

Expression of extracellular matrix protein in advanced keratoconus and the normal human cornea.

作者信息

Habroosh Fatima, Filippini Perla, Al Saadi Ahmed, Soliman Shady, Yildiz Burcin Kepez, Sahay Prity, Said Dalia G, Dua Harminder S

机构信息

Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom.

Department of Ophthalmology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

出版信息

Front Med (Lausanne). 2025 Aug 5;12:1612452. doi: 10.3389/fmed.2025.1612452. eCollection 2025.

DOI:10.3389/fmed.2025.1612452
PMID:40837574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12361212/
Abstract

BACKGROUND

The pre-Descemet layer (Dua's layer) (PDL/DL) and the Descemet membrane (DM) have the highest expression of elastin in normal corneas. Reduced expression of elastin occurs in the corneal stroma of patients with keratoconus (KC). This study aimed to examine the expression of elastin and that of other extracellular matrix (ECM) components, and proteoglycan proteins in the PDL/DL and DM in advanced KC.

METHODS

Corneal tissue obtained from four subjects with KC who underwent penetrating keratoplasty was compared with tissue from four normal corneas. The tissues were sectioned and analyzed with specific markers for extracellular matrix proteins and proteoglycans-namely, elastin, collagens I, IV, and VI, fibulin-2, and decorin-using immunohistochemical analysis. Fluorescence intensity was measured using ImageJ software and compared to controls.

RESULTS

The expression of elastin was significantly reduced in the PDL/DL and DM in KC cases compared to controls. Concurrently, an increased expression of elastin was noted anteriorly in the subepithelial region. Expression of collagen IV, collagen VI, and decorin was reduced in the PDL/DL and DM, whereas expression of collagen I and fibulin-2 was unaltered in KC cases compared to controls.

CONCLUSION

The significant reduction of elastin in the PDL/DL and DM in cases of advanced keratoconus with acute corneal hydrops (ACH) may play a crucial role in the pathology of KC and the subsequent onset of ACH. Furthermore, elastin is considered to be pivotal in the disease progression, as keratoconus typically starts with a posterior elevation affecting these two layers.

摘要

背景

前弹力层(杜阿层)(PDL/DL)和后弹力层(DM)在正常角膜中弹性蛋白表达最高。圆锥角膜(KC)患者角膜基质中弹性蛋白表达降低。本研究旨在检测晚期KC患者PDL/DL和DM中弹性蛋白以及其他细胞外基质(ECM)成分和蛋白聚糖蛋白的表达。

方法

将4例接受穿透性角膜移植术的KC患者的角膜组织与4例正常角膜组织进行比较。将组织切片,并用细胞外基质蛋白和蛋白聚糖的特异性标志物,即弹性蛋白、I型、IV型和VI型胶原蛋白、纤维连接蛋白-2和核心蛋白聚糖,进行免疫组织化学分析。使用ImageJ软件测量荧光强度并与对照组进行比较。

结果

与对照组相比,KC患者PDL/DL和DM中弹性蛋白的表达显著降低。同时,上皮下区域前部弹性蛋白表达增加。与对照组相比,KC患者PDL/DL和DM中IV型胶原蛋白、VI型胶原蛋白和核心蛋白聚糖的表达降低,而I型胶原蛋白和纤维连接蛋白-2的表达未改变。

结论

晚期圆锥角膜合并急性角膜水肿(ACH)患者PDL/DL和DM中弹性蛋白的显著减少可能在KC的病理过程及随后ACH的发生中起关键作用。此外,弹性蛋白被认为在疾病进展中起关键作用,因为圆锥角膜通常始于影响这两层的后凸。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/12361212/3ba8231f9750/fmed-12-1612452-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/12361212/905e745fa756/fmed-12-1612452-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/12361212/1baf35842806/fmed-12-1612452-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/12361212/3ba8231f9750/fmed-12-1612452-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/12361212/905e745fa756/fmed-12-1612452-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/12361212/1baf35842806/fmed-12-1612452-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/12361212/3ba8231f9750/fmed-12-1612452-g003.jpg

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本文引用的文献

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The pre-Descemet's layer (Dua's layer, also known as the Dua-Fine layer and the pre-posterior limiting lamina layer): Discovery, characterisation, clinical and surgical applications, and the controversy.前 Descemet 层(Dua 层,也称为 Dua-Fine 层和前后限制层):发现、特征、临床和手术应用以及争议。
Prog Retin Eye Res. 2023 Nov;97:101161. doi: 10.1016/j.preteyeres.2022.101161. Epub 2023 Jan 14.
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Keratoconus: An updated review.圆锥角膜:更新综述。
Cont Lens Anterior Eye. 2022 Jun;45(3):101559. doi: 10.1016/j.clae.2021.101559. Epub 2022 Jan 4.
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Keratoconus: Diagnosis and Staging.
圆锥角膜:诊断与分期。
Cornea. 2022 Jan 1;41(1):1-11. doi: 10.1097/ICO.0000000000002781.
4
The Influence of Speed During Stripping in Descemet Membrane Endothelial Keratoplasty Tissue Preparation.撕囊时的速度对撕囊在准备 Descemet 膜内皮角膜移植术中的影响。
Cornea. 2020 Sep;39(9):1086-1090. doi: 10.1097/ICO.0000000000002338.
5
Are Descemet Membrane Ruptures the Root Cause of Corneal Hydrops in Keratoconic Eyes?圆锥角膜眼中后弹力层破裂是角膜水肿的根本原因吗?
Am J Ophthalmol. 2019 Sep;205:204. doi: 10.1016/j.ajo.2019.04.038. Epub 2019 Jul 8.
6
Are Descemet Membrane Ruptures the Root Cause of Corneal Hydrops in Keratoconic Eyes?Descemet 膜破裂是否是圆锥角膜眼中角膜水肿的根本原因?
Am J Ophthalmol. 2019 Sep;205:147-152. doi: 10.1016/j.ajo.2019.03.017. Epub 2019 Mar 22.
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Biobanking of Dehydrated Human Donor Corneal Stroma to Increase the Supply of Anterior Lamellar Grafts.脱水人供体角膜基质的生物样本库建设以增加前板层移植片的供应
Cornea. 2019 Apr;38(4):480-484. doi: 10.1097/ICO.0000000000001876.
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Elastin Content and Distribution in Endothelial Keratoplasty Tissue Determines Direction of Scrolling.内皮角膜移植组织中的弹性蛋白含量和分布决定了组织的卷动方向。
Am J Ophthalmol. 2018 Oct;194:16-25. doi: 10.1016/j.ajo.2018.07.001. Epub 2018 Jul 17.
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A review of keratoconus: Diagnosis, pathophysiology, and genetics.圆锥角膜的综述:诊断、病理生理学和遗传学。
Surv Ophthalmol. 2017 Nov-Dec;62(6):770-783. doi: 10.1016/j.survophthal.2017.06.009. Epub 2017 Jul 6.
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Elastic microfibril distribution in the cornea: Differences between normal and keratoconic stroma.弹性微原纤维在角膜中的分布:正常角膜基质与圆锥角膜基质的差异。
Exp Eye Res. 2017 Jun;159:40-48. doi: 10.1016/j.exer.2017.03.002. Epub 2017 Mar 14.