Adenoviral reporter gene transfer to the human trabecular meshwork does not alter aqueous humor outflow.: Relevance for potential gene therapy of glaucoma
Adenoviral reporter gene transfer to the human trabecular meshwork does not alter aqueous humor outflow.: Relevance for potential gene therapy of glaucoma
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DOI：
10.1038/sj.gt.3300860
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发表时间：
1999-04-01
期刊：
影响因子：
5.1
通讯作者：
Epstein, DL
中科院分区：
文献类型：
--
作者：
Borrás, T;Rowlette, LL;Epstein, DL
从眼前房流出的房水的阻塞导致青光眼的眼内压升高，青光眼是世界范围内失明的第二大原因。我们的目标是能够通过基因转移到小梁网（TM）细胞来调节房水流出阻力。我们以前已经表明，腺病毒载体能够转移一个报告基因的TIW的死后人类捐助者。然而，评估青光眼的基因治疗需要能够监测房水流出设施（C=流量/压力）变化的模型。在这项研究中，我们使用了四个复制缺陷型腺病毒在两个这样的灌注模型。在第一个模型中，整个猪眼被感染，在恒定压力下灌注并记录流量变化5 h。在第二个实验中，感染人眼前节，以恒定流量和压力变化记录灌注3天。单剂量10（8）腺病毒鼠疫形成单位（pfu）引起C减少，而单剂量10（7）、10（6）和10（5）p.f.u.不影响流出道设施，保持阳性基因转移。这些发现表明，在有效剂量下，腺病毒可以成为有用的载体，用于青光眼的基因治疗。
Obstruction of the aqueous humor outflow from the anterior chambers of the eye leads to an elevation of intraocular pressure in glaucoma, the second major cause of blindness world-wide. Our goal is to be able to modulate aqueous humor outflow resistance by gene transfer to the cells of the trabecular meshwork (TM). We have previously shown that adenoviral vectors are able to transfer a reporter gene to the TIW of post-mortem human donors. However, assessing gene therapy for glaucoma requires models that can monitor changes in aqueous humor outflow facility (C=flow/pressure). In this study we used four replication-deficient adenoviruses in two such perfusion models. In the first model, whole porcine eyes were infected, perfused at constant pressure and flow changes recorded for 5 h. In the second one, anterior segments from human eyes were infected, perfused at constant flow and pressure changes recorded for 3 days. A single dose of 10(8) adenovirus plague forming units (pfu) causes a reduction in C while single doses of 10(7), 10(6) and 10(5) p.f.u. do not affect outflow facility and retain positive gene transfer. These findings indicate that adenovirus, at effective doses, could become useful vectors for gene therapy of glaucoma.