Increased matrix metalloproteinases 1, 2, and 3 in the monkey uveoscleral outflow pathway after topical prostaglandin F(2 alpha)-isopropyl ester treatment.

Increased matrix metalloproteinases 1, 2, and 3 in the monkey uveoscleral outflow pathway after topical prostaglandin F(2 alpha)-isopropyl ester treatment.
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局部前列腺素 F(2α)-异丙酯治疗后,猴葡萄膜巩膜流出途径中的基质金属蛋白酶 1、2 和 3 增加。

DOI:
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发表时间:
2001
期刊:
A M A Archives of Ophthalmology
影响因子:
--
通讯作者:
R. Weinreb
R. Weinreb
中科院分区:
--
文献类型:
--
作者:
D. Gaton;T. Sagara;J. Lindsey;B. Gabelt;P. Kaufman;R. Weinreb

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目的 研究局部给予前列腺素F(2 α)-异丙酯(PGF(2 α)-IE)对猴眼前段组织内基质金属蛋白酶(MMPs)1、2和3免疫反应性的影响。 方法 评价了4只食蟹猴的8只眼睛。用2 mg PGF(2 α)-IE每天两次处理每只猴子的一只眼睛,持续5天,并测量眼内压降低。固定和处理后,使用MMP-1(间质胶原酶)、MMP-2(明胶酶A)或MMP-3(基质溶解素-1)的抗体对前段的脱蜡切片进行免疫染色。采用成像密度测定法测量虹膜根部、睫状肌和邻近巩膜上垂直于其长轴的沿着2条线段的光密度。 结果 与对侧赋形剂处理的眼睛相比,在虹膜根部、睫状肌和邻近巩膜中观察到所有3种MMP的光密度分数的统计学显著增加(P<0.01)。在这些组织中,MMP-1免疫反应性分别增加了89% +/-16%、61% +/-8%和66% +/-57%,MMP-2免疫反应性分别增加了129% +/-53%、82% +/-27%和267% +/-210%;和MMP-3免疫反应性分别降低207% ± 84%、83% ± 49%和726% ± 500%。 结论 用PGF(2 α)-IE处理猴眼诱导葡萄膜巩膜流出途径组织中MMP-1、MMP-2和MMP-3升高。这些增加表明MMPs可能在局部前列腺素治疗观察到的葡萄膜巩膜流出增加中起重要作用。 临床相关性 PGF(2 α)-IE局部治疗后,猴葡萄膜巩膜流出途径组织中MMPs的免疫反应性增加。这种反应也可能与其他用于治疗青光眼的前列腺素类药物的降眼压作用有关。
OBJECTIVE To investigate the effects of topical prostaglandin F(2 alpha)--isopropyl ester (PGF(2 alpha)-IE) administration on immunoreactivity of matrix metalloproteinases (MMPs) 1, 2, and 3 within the anterior segment tissues of monkey eyes. METHODS Eight eyes from 4 cynomolgus monkeys were evaluated. One eye from each monkey was treated with 2 mg of PGF(2 alpha)-IE twice daily for 5 days, and intraocular pressure reduction was measured. After fixation and processing, deparaffinized sections of anterior segments were immunostained using antibodies to MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), or MMP-3 (stromelysin-1). Optical density along 2 line segments overlying the iris root, ciliary muscle, and adjacent sclera and perpendicular to their long axes was measured using imaging densitometry. RESULTS Compared with the contralateral vehicle-treated eyes, statistically significant increases in optical density scores were observed in the iris root, ciliary muscle, and adjacent sclera for all 3 MMPs (P<.01). In these tissues, MMP-1 immunoreactivity was increased by a mean +/- SD of 89% +/- 16%, 61% +/- 8%, and 66% +/- 57%, respectively; MMP-2 immunoreactivity by 129% +/- 53%, 82% +/- 27%, and 267% +/- 210%, respectively; and MMP-3 immunoreactivity by 207% +/- 84%, 83% +/- 49%, and 726% +/- 500%, respectively. CONCLUSIONS Treatment of monkey eyes with PGF(2 alpha)-IE induces elevation of MMP-1, MMP-2, and MMP-3 in tissues of the uveoscleral outflow pathway. These increases suggest that MMPs might play an important role in the increased uveoscleral outflow observed with topical prostaglandin treatment. CLINICAL RELEVANCE Immunoreactivity of MMPs in tissues of the monkey uveoscleral outflow pathway is increased after topical treatment with PGF(2 alpha)-IE. This response also might be involved in the intraocular pressure--lowering effect of other prostanoids used to treat glaucoma.
DOI: 10.3109/02713689609017628
发表时间: 1996-08-01
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作者:
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通讯作者: Weinreb, RN
DOI: --
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DOI: --
发表时间: 1997
影响因子: 4.4
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DOI: --
发表时间: 1999
影响因子: 4.4
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