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核黄素/紫外线 A 巩膜胶原交联术对近视豚鼠局部巩膜厚度和 MMP-2、MT1-MMP 表达的影响。

Effects of riboflavin/ultraviolet-A scleral collagen cross-linking on regional scleral thickness and expression of MMP-2 and MT1-MMP in myopic guinea pigs.

机构信息

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

出版信息

PLoS One. 2023 Jan 18;18(1):e0279111. doi: 10.1371/journal.pone.0279111. eCollection 2023.

DOI:10.1371/journal.pone.0279111
PMID:36652495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9847964/
Abstract

OBJECTIVE

To investigate the effects of scleral collagen cross-linking (SXL) using riboflavin and ultraviolet A (UVA) light on the scleral thickness of different regions and expression of matrix metalloproteinase 2 (MMP-2) and membrane-type MMP-1 (MT1-MMP) in guinea pigs with lens-induced myopia.

METHODS

Forty-eight 4-week-old guinea pigs were assigned to three groups (n = 16 per group): SXL group, lens-induced myopia (LIM) group, and control group. The sclera of the right eye of the guinea pig in the SXL group was surgically exposed, riboflavin was dropped on the treatment area for 10 minutes before the 30-minute UVA irradiation. The same surgical procedure was performed in the LIM group without UVA irradiation. The -10.00 D lenses were then placed on the right eyes of guinea pigs in the SXL and LIM groups for six weeks. The control group received no treatment. The left eyes were untreated in all groups. The ocular axial length (AXL) and refraction were measured at 4 weeks and 10 weeks of age. 10-week-old guinea pigs were sacrificed, and the right eyes were enucleated and evenly divided for preparation of hematoxylin and eosin (HE) stained sections, quantitative real-time polymerase chain reaction (qPCR) and western blotting. The scleral thickness of different regions was measured on HE stained sections. The temporal half of the sclera was harvested to measure the expression of MMP-2 and MT1-MMP by qPCR and western blotting.

RESULTS

The AXL was significantly shorter, and the degree of myopic refraction was significantly lower in the SXL group than those in the LIM group at 10 weeks of age. The scleral thickness of the cross-linked area was significantly greater in the SXL group than that of the corresponding area in the LIM group, while the scleral thickness of the untreated nasal side was not significantly different between the SXL group and the LIM group. The expression of MMP-2 and MT1-MMP of the cross-linked sclera was significantly downregulated compared with that of the corresponding area in the LIM group.

CONCLUSION

Riboflavin/UVA SXL could slow myopia progression and thicken the cross-linked sclera in guinea pigs, which might be related to the downregulation of MMP-2 and MT1-MMP expression during the scleral remodeling process.

摘要

目的

研究核黄素/紫外线 A(UVA)交联(SXL)对诱导性近视豚鼠巩膜不同区域厚度及基质金属蛋白酶 2(MMP-2)和膜型 MMP-1(MT1-MMP)表达的影响。

方法

将 48 只 4 周龄豚鼠随机分为 3 组(每组 16 只):SXL 组、诱导性近视(LIM)组和对照组。SXL 组豚鼠右眼行巩膜暴露手术,UVA 照射前 10 分钟滴注核黄素于治疗区,LIM 组行相同手术但不进行 UVA 照射。然后在 SXL 和 LIM 组豚鼠右眼放置-10.00 D 镜片 6 周。对照组不做任何处理。所有组的左眼均未处理。4 周和 10 周龄时测量眼轴(AXL)和屈光度。10 周龄时处死豚鼠,右眼眼球摘出并均等分为两份,分别用于制备苏木精和伊红(HE)染色切片、实时定量聚合酶链反应(qPCR)和 Western 印迹。在 HE 染色切片上测量不同区域的巩膜厚度。采集巩膜的颞侧半部分,通过 qPCR 和 Western 印迹测量 MMP-2 和 MT1-MMP 的表达。

结果

与 LIM 组相比,SXL 组在 10 周龄时 AXL 明显缩短,近视屈光度明显降低。SXL 组交联区巩膜厚度明显大于 LIM 组相应区域,而 SXL 组未处理鼻侧巩膜厚度与 LIM 组无显著差异。交联巩膜的 MMP-2 和 MT1-MMP 表达明显低于 LIM 组相应区域。

结论

核黄素/UVA SXL 可减缓豚鼠近视进展并使交联巩膜增厚,这可能与巩膜重塑过程中 MMP-2 和 MT1-MMP 表达下调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/5bd33d95b596/pone.0279111.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/e1a0a3c191fe/pone.0279111.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/980e32f5ea3d/pone.0279111.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/aa5dba25a4be/pone.0279111.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/c23e873ae22c/pone.0279111.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/e9b4f72ba601/pone.0279111.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/5bd33d95b596/pone.0279111.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/e1a0a3c191fe/pone.0279111.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/980e32f5ea3d/pone.0279111.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/aa5dba25a4be/pone.0279111.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/c23e873ae22c/pone.0279111.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/e9b4f72ba601/pone.0279111.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/9847964/5bd33d95b596/pone.0279111.g006.jpg

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