Disruption of fibronectin fibrillogenesis affects intraocular pressure (IOP) in BALB/cJ mice
Disruption of fibronectin fibrillogenesis affects intraocular pressure (IOP) in BALB/cJ mice
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DOI：
10.1371/journal.pone.0237932
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发表时间：
2020-08-21
期刊：
影响因子：
3.7
通讯作者：
Peters, Donna M.
中科院分区：
文献类型：
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作者：
Faralli, Jennifer A.;Filla, Mark S.;Peters, Donna M.
TGF β 2引起的含有EDA+纤连蛋白的纤连蛋白原纤维沉积的增加被认为与通过眼小梁网（TM）的房水流出减少和在原发性开角型青光眼（POAG）中观察到的眼内压（IOP）升高有关。使用一种称为FUD的纤连蛋白结合肽，它可以破坏纤连蛋白原纤维形成，我们研究了在TGF β 2 BALB/cJ小鼠高眼压模型中，破坏纤连蛋白原纤维形成是否会影响IOP。玻璃体内注射表达生物活性TGF β 2的腺病毒（Ad 5）的BALB/cJ小鼠（226/228）在2周后显示出IOP的显著增加。当在Ad 5-TGF β 2注射后2周将1 μ M FUD前房内注射到小鼠中时，FUD在2天后显著降低IOP。突变的FUD（mFUD）和PBS对IOP均无任何影响。注射FUD后4天，IOP恢复至FUD注射前水平。在缺乏TGF β 2的情况下，前房内注射FUD对IOP没有影响。表达TGF β 2的小鼠眼前节的蛋白质印迹显示，前房注射后2天FUD降低了纤维连接蛋白水平（p
Increased deposition of fibronectin fibrils containing EDA+fibronectin by TGF beta 2 is thought to be involved in the reduction of aqueous humor outflow across the trabecular meshwork (TM) of the eye and the elevation in intraocular pressure (IOP) observed in primary open angle glaucoma (POAG). Using a fibronectin-binding peptide called FUD that can disrupt fibronectin fibrillogenesis, we examined if disrupting fibronectin fibrillogenesis would affect IOP in the TGF beta 2 BALB/cJ mouse model of ocular hypertension. BALB/cJ mice that had been intravitreally injected with an adenovirus (Ad5) expressing a bioactive TGF beta 2(226/228)showed a significant increase in IOP after 2 weeks. When 1 mu M FUD was injected intracamerally into mice 2 weeks post Ad5-TGF beta 2 injection, FUD significantly reduced IOP after 2 days. Neither mutated FUD (mFUD) nor PBS had any effect on IOP. Four days after FUD was injected, IOP returned to pre-FUD injection levels. In the absence of TGF beta 2, intracameral injection of FUD had no effect on IOP. Western blotting of mouse anterior segments expressing TGF beta 2 showed that FUD decreased fibronectin levels 2 days after intracameral injection (p