Effects of Lentivirus-Mediated C3 Expression on Trabecular Meshwork Cells and Intraocular Pressure.
Effects of Lentivirus-Mediated C3 Expression on Trabecular Meshwork Cells and Intraocular Pressure.
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慢病毒介导的C3表达对小梁网细胞和眼压的影响
DOI：
10.1167/iovs.18-24978
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发表时间：
2018-10-01
影响因子：
4.4
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Tan J;Fan N;Wang N;Feng B;Yang M;Liu G;Wang Y;Zhu X;Kaufman PL;Pang IH;Liu X
目的探讨慢病毒介导的外酶C3转移酶(C3)在体外培养的人眼小梁细胞(HTM)中的表达及其对大鼠眼压的影响。方法用单独表达绿色荧光蛋白(GFP)的慢病毒载体(LV-GFP)或绿色荧光蛋白与C3共表达的慢病毒载体(LV-C3-GFP)处理HTM细胞。观察细胞形态和肌动蛋白应激纤维的变化。将载体注射到大鼠前房内，用Micron III视网膜成像显微镜和荧光显微镜观察GFP的表达。用回弹式眼压计监测大鼠眼压的变化，用裂隙灯评估眼压。结果LV介导的C3表达可诱导HTM细胞形态发生改变。细胞变得回缩和变圆。注射LV-C3-GFP或LV-GFP后8~48天，观察大鼠前房角GFP的表达。与对侧对照眼(LV-GFP组)或注射前的同侧基线相比，LV-C3-GFP组的眼压在注射后3天开始显著降低，并持续至少40天(P<；0.05)。LV-C3-GFP组和LV-GFP组均未见明显炎症征象。结论LV介导的C3表达可诱导HTM细胞形态发生改变。房内注射LV-C3-GFP可使大鼠眼压下降至少40天。LV-C3-GFP组和LV-GFP组均未见明显炎症反应。本研究支持C3基因治疗青光眼的可能性。
Purpose We evaluated the effects of lentivirus-mediated exoenzyme C3 transferase (C3) expression on cultured primary human trabecular meshwork (HTM) cells in vitro, and on rat intraocular pressure (IOP). Methods HTM cells were cultured and treated with lentivirus vectors expressing either green fluorescent protein (GFP) only (LV-GFP) or GFP and C3 together (LV-C3-GFP). Changes in cell morphology and actin stress fibers were assessed. The vectors were also injected into the anterior chamber of rats, and GFP expression was visualized by a Micron III Retinal Imaging Microscope in vivo and a fluorescence microscope ex vivo. Changes in rat IOP were monitored by using a rebound tonometer and the eyes were evaluated by slit lamp. Results LV-mediated C3 expression induced morphologic changes in HTM cells. The cells became retracted and rounded. GFP expression in the anterior chamber angle of rats was observed in vivo from 8 days to 48 days after injection of LV-C3-GFP or LV-GFP. IOP was significantly decreased in the LV-C3-GFP group starting 3 days post injection, and lasting for at least 40 days, when compared to either the contralateral control eyes (the LV-GFP group) or the ipsilateral baseline before injection (P < 0.05). No obvious inflammatory signs were observed in either the LV-C3-GFP or LV-GFP groups. Conclusions LV-mediated C3 expression induced changes in morphology of cultured HTM cells. Intracameral injection of LV-C3-GFP lowered rat IOP for at least 40 days. No significant inflammatory reactions were observed in either the LV-C3-GFP or LV-GFP groups. This study supports the possible use of C3 gene therapy for the treatment of glaucoma.
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影响因子：
4.4
作者：
Loewen RT;Roy P;Park DB;Jensen A;Scott G;Cohen-Karni D;Fautsch MP;Schuman JS;Loewen NA
通讯作者：
Loewen NA
影响因子：
--
作者：
Jacobson, Samuel G.;Cideciyan, Artur V.;Ratnakaram, Ramakrishna;Heon, Elise;Schwartz, Sharon B.;Roman, Alejandro J.;Peden, Marc C.;Aleman, Tomas S.;Boye, Sanford L.;Sumaroka, Alexander;Conlon, Thomas J.;Calcedo, Roberto;Pang, Ji-Jing;Erger, Kirsten E.;Olivares, Melani B.;Mullins, Cristina L.;Swider, Malgorzata;Kaushal, Shalesh;Feuer, William J.;Iannaccone, Alessandro;Fishman, Gerald A.;Stone, Edwin M.;Byrne, Barry J.;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
4.6
作者：
Kaneko Y;Ohta M;Inoue T;Mizuno K;Isobe T;Tanabe S;Tanihara H
通讯作者：
Tanihara H
影响因子：
2
作者：
Lee ES;Rasmussen CA;Filla MS;Slauson SR;Kolb AW;Peters DM;Kaufman PL;Gabelt BT;Brandt CR
通讯作者：
Brandt CR
影响因子：
5.1
作者：
McCarty, DM;Monahan, PE;Samulski, RJ
通讯作者：
Samulski, RJ