Effect of αvβ3 Integrin Expression and Activity on Intraocular Pressure
Effect of αvβ3 Integrin Expression and Activity on Intraocular Pressure
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DOI：
10.1167/iovs.18-26038
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发表时间：
2019-04-01
影响因子：
4.4
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.;Fills, Mark S.;Peters, Donna M.
目的.目的：探讨α v β 3整合素的表达和激活对眼内压（IOP）的影响。Cre（+/-）β 3（flox/flox）小鼠用局部他莫昔芬滴眼液处理5天以激活Cre并从眼前节切除β 3整联蛋白基因。使用反跳眼压计每周测量IOP，持续11周。然后杀死小鼠，并使用蛋白质印迹分析和免疫荧光显微术测定Cre（+/-）β 3（flox/flox）小鼠中β 3整联蛋白亚基表达的变化。为了确定α v β 3整联蛋白活化对流出设施的影响，用α v β 3整联蛋白活化抗体AP 5或同种型IgG对照灌注猪器官培养前段（POCAS）21小时。在前房内输注AP 5、AP 3、IgG或PBS的C57 BL/6 J小鼠中，在7天内测量α v β 3整联蛋白活化对IOP的影响。使用他莫昔芬诱导的Cre-loxP系统删除β 3整联蛋白亚基导致小梁网和睫状肌中β 3整联蛋白亚基的表达减少。在形态学上未检测到眼前节的大体变化。β 3整合素亚基的缺失导致在他莫昔芬治疗后2周内小鼠的IOP显著（P < 0.05）降低，并持续11周。用AP 5抗体激活α v β 3整合素导致C57 BL/6 J小鼠的IOP显著增加（P < 0.05），42%的POCAS的流出道灵活性降低。这些研究证实了α v β 3整联蛋白信号传导在IOP调节中的作用。
PURPOSE. To determine the effects of alpha v beta 3 integrin expression and activation on intraocular pressure (IOP).METHODS. Cre(+/-)beta 3(flox/flox) mice were treated with topical tamoxifen eye drops for 5 days to activate Cre and excise the beta 3 integrin gene from the anterior segment. IOP was measured weekly for 11 weeks using rebound tonometry. Mice were then killed and changes in expression of the beta 3 integrin subunit in Cre(+/-) beta 3(flox/flox) mice were determined using Western blotting analysis and immunofluorescence microscopy. To determine the effect of alpha v beta 3 integrin activation on outflow facility, porcine organ culture anterior segments (POCAS) were perfused with the alpha v beta 3 integrin-activating antibody AP5 or an isotype IgG control for 21 hours. The effect of alpha v beta 3 integrin activation on IOP was measured over 7 days in C57BL/6J mice intracamerally infused with AP5, AP3, IgG, or PBS.RESULTS. Deletion of the beta 3 integrin subunit using the tamoxifen-inducible Cre-loxP system resulted in a decrease in expression of the beta 3 integrin subunit in the trabecular meshwork and ciliary muscle. Morphologically no gross changes in the anterior segment were detected. Deletion of the beta 3 integrin subunit resulted in a significantly (P < 0.05) lower IOP in mice within 2 weeks following the tamoxifen treatment and persisted for 11 weeks. Activating the alpha v beta 3 integrin with the AP5 antibody resulted in a significant (P < 0.05) increase in IOP in C57BL/6J mice and a decrease in outflow facility in 42% of the POCAS.CONCLUSIONS. These studies demonstrate a role for alpha v beta 3 integrin signaling in the regulation of IOP.