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前列腺素 F2α 类似物对角膜滞后和细胞外基质金属蛋白酶 3 和 9 表达的影响。

Influence of a Prostaglandin F2α Analogue on Corneal Hysteresis and Expression of Extracellular Matrix Metalloproteinases 3 and 9.

机构信息

Department of Ophthalmology, University of Bonn, Bonn, Germany.

Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.

出版信息

Transl Vis Sci Technol. 2023 May 1;12(5):28. doi: 10.1167/tvst.12.5.28.

DOI:10.1167/tvst.12.5.28
PMID:37233995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10226607/
Abstract

PURPOSE

Low corneal hysteresis (CH) is associated with an increased risk of glaucoma. Prostaglandin analogue (PGA) eye drops may exert their intraocular pressure (IOP)-lowering effect partially by increasing CH.

METHODS

Twelve pairs of organ-cultured human donor corneas were used in an ex vivo model. In each case, one cornea was treated with PGA (Travoprost) for 30 days, whereas the other served as an untreated control. IOP levels were simulated in an artificial anterior chamber model. CH was measured using the Ocular Response Analyzer (ORA). Corneal expression of matrix-metalloproteinases (MMPs) was assessed by immunhistochemistry and real-time polymerase chain reaction (RT-PCR).

RESULTS

Increased CH was observed in the PGA-treated corneas. However, at IOP between 10 and 20 mm Hg, CH was increased in PGA-treated corneas (13.12 ± 0.63 mm Hg; control: 12.34 ± 0.49 mm Hg), although not significantly (P = 0.14). CH was significantly increased at higher IOP levels (21-40 mm Hg; PGA-treated: 17.62 ± 0.40 mm Hg; control: 11.60 ± 0.39, P < 0.0001). Treatment with PGA resulted in increased expression of MMP-3 and MMP-9.

CONCLUSIONS

CH was increased after exposure to PGA. However, this increase was significant only in eyes with higher IOP (>21 mm Hg). A significant increase in MMP-3 and -9 was observed in PGA-treated corneas, indicating structural changes in corneal biomechanics caused by PGA.

TRANSLATIONAL RELEVANCE

PGAs alter biomechanical structures by directly upregulating MMP-3 and -9, and the increase in CH is dependent on the level of IOP. Therefore, PGAs may have a greater effect when baseline IOP is higher.

摘要

目的

低角膜滞后(CH)与青光眼风险增加有关。前列腺素类似物(PGA)眼药水可能通过增加 CH 部分发挥其降低眼压(IOP)的作用。

方法

在离体模型中使用了 12 对器官培养的人供体角膜。在每种情况下,一只角膜用 PGA(曲伏前列素)治疗 30 天,而另一只作为未经处理的对照。在人工前房模型中模拟 IOP 水平。使用眼反应分析仪(ORA)测量 CH。通过免疫组织化学和实时聚合酶链反应(RT-PCR)评估角膜基质金属蛋白酶(MMPs)的表达。

结果

在 PGA 处理的角膜中观察到 CH 增加。然而,在 IOP 为 10 至 20mmHg 之间时,PGA 处理的角膜中的 CH 增加(13.12±0.63mmHg;对照:12.34±0.49mmHg),尽管没有显著差异(P=0.14)。在较高的 IOP 水平(21-40mmHg)时,CH 显著增加(PGA 处理:17.62±0.40mmHg;对照:11.60±0.39mmHg,P<0.0001)。PGA 治疗导致 MMP-3 和 MMP-9 的表达增加。

结论

暴露于 PGA 后 CH 增加。然而,这种增加仅在 IOP 较高的眼睛中(>21mmHg)显著。在 PGA 处理的角膜中观察到 MMP-3 和 -9 的明显增加,表明 PGA 引起角膜生物力学结构的变化。

翻译

角膜滞后(CH)是一种用于评估角膜弹性的指标,用于评估角膜对眼压变化的反应能力。

PGA 是一种前列腺素类似物,常用于治疗青光眼等眼部疾病。

在这项研究中,研究人员使用了离体的人眼角膜样本,将一部分角膜暴露于 PGA 中,另一部分作为对照。

研究结果表明,PGA 处理后的角膜 CH 增加,但只有在 IOP 较高时才具有统计学意义。

此外,PGA 处理后的角膜中 MMP-3 和 MMP-9 的表达也增加,这表明 PGA 可能通过直接上调 MMP-3 和 MMP-9 来改变角膜的生物力学结构。

总之,这项研究表明,PGA 可能通过增加 MMP-3 和 MMP-9 的表达来改变角膜的生物力学结构,从而增加 CH。此外,这种增加在 IOP 较高时更为明显,这可能有助于解释为什么 PGA 在治疗青光眼等疾病时更为有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/3facb2a0db94/tvst-12-5-28-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/6bd0741ca2d8/tvst-12-5-28-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/6c29a7c12790/tvst-12-5-28-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/118be5c9ea9b/tvst-12-5-28-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/585aad3726d6/tvst-12-5-28-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/3facb2a0db94/tvst-12-5-28-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/6bd0741ca2d8/tvst-12-5-28-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/6c29a7c12790/tvst-12-5-28-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/118be5c9ea9b/tvst-12-5-28-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/585aad3726d6/tvst-12-5-28-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d54/10226607/3facb2a0db94/tvst-12-5-28-f005.jpg

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