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拉坦前列素和噻吗洛尔对人结膜组织病理学的影响。

Effect of latanoprost and timolol on the histopathology of the human conjunctiva.

作者信息

Terai N, Schlötzer-Schrehardt U, Lampel J, Böhm A G, Rummelt C, Schmidt E, Pillunat L E

机构信息

Department of Ophthalmology, Carl Gustav Carus University Hospital, Fetscherstrasse 74, Dresden, Germany.

出版信息

Br J Ophthalmol. 2009 Feb;93(2):219-24. doi: 10.1136/bjo.2008.140186. Epub 2008 Oct 29.

Abstract

AIM

To investigate the effect of timolol and latanoprost on the extracellular matrix organisation, inflammatory infiltration, and expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the human conjunctiva.

METHODS

Conjunctival biopsies were obtained from the inferior fornix during routine cataract surgery from 20 patients with primary open-angle glaucoma, who had received a monotherapy either with timolol or latanoprost, and from 10 non-glaucomatous patients. Specimens were investigated by light microscopy, immunohistochemistry using antibodies against MMP-1,-3, TIMP-2,-3 and CD 68 antibodies and by quantitative transmission electron microscopy.

RESULTS

The number of collagen fibres was significantly decreased in latanoprost-treated conjunctival specimens compared with timolol-treated eyes (p<0.01) but showed no difference to controls. Amorphous material was increased in both treated groups compared with controls (p<0.001) but was less in latanoprost-treated specimens compared with timolol-treated eyes (p<0.001). Optically clear spaces, probably containing glycosaminoglycans, were significantly reduced in both treated groups-with less of a reduction in latanoprost-compared with timolol-treated eyes (p<0.001). A marked upregulation of MMP-1 and MMP-3 and moderately increased staining for TIMP-2 and TIMP-3 was found in epithelial cells and subepithelial stromal cells of latanoprost-treated eyes. A moderate infiltration with macrophages and inflammatory cells was observed in timolol-treated eyes.

CONCLUSIONS

Latanoprost-treated conjunctival specimens showed a decreased stromal collagen density and a less pronounced inflammatory infiltration. The upregulation of MMP-1 and MMP-3 in latanoprost-treated eyes might explain the reduced extracellular matrix accumulation in the conjunctival stroma. Therefore, latanoprost therapy might have a more favourable effect on the outcome of glaucoma filtering surgery.

摘要

目的

研究噻吗洛尔和拉坦前列素对人结膜细胞外基质组织、炎性浸润以及基质金属蛋白酶(MMPs)和基质金属蛋白酶组织抑制剂(TIMPs)表达的影响。

方法

从20例接受噻吗洛尔或拉坦前列素单一疗法的原发性开角型青光眼患者以及10例非青光眼患者的常规白内障手术中获取下穹窿结膜活检组织。通过光学显微镜、使用抗MMP-1、-3、TIMP-2、-3抗体和CD 68抗体的免疫组织化学以及定量透射电子显微镜对标本进行研究。

结果

与噻吗洛尔治疗的眼睛相比,拉坦前列素治疗的结膜标本中胶原纤维数量显著减少(p<0.01),但与对照组无差异。与对照组相比,两个治疗组中的无定形物质均增加(p<0.001),但与噻吗洛尔治疗的眼睛相比,拉坦前列素治疗的标本中无定形物质较少(p<0.001)。两个治疗组中可能含有糖胺聚糖的光学透明间隙均显著减少,与噻吗洛尔治疗的眼睛相比,拉坦前列素组减少程度较小(p<0.001)。在拉坦前列素治疗的眼睛的上皮细胞和上皮下基质细胞中发现MMP-1和MMP-3明显上调,TIMP-2和TIMP-3染色适度增加。在噻吗洛尔治疗的眼睛中观察到巨噬细胞和炎性细胞的中度浸润。

结论

拉坦前列素治疗的结膜标本显示基质胶原密度降低,炎性浸润不明显。拉坦前列素治疗的眼睛中MMP-1和MMP-3的上调可能解释了结膜基质中细胞外基质积累的减少。因此,拉坦前列素治疗可能对青光眼滤过手术的结果有更有利的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c641/2628534/0ff35ab3cba8/BJ1-93-02-0219-f01.jpg

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