Non-invasive observation of repeated adenoviral GFP gene delivery to the anterior segment of the monkey eye in vivo
Non-invasive observation of repeated adenoviral GFP gene delivery to the anterior segment of the monkey eye in vivo
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DOI：
10.1002/jgm.210
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发表时间：
2001-09-01
影响因子：
3.5
通讯作者：
Kaufman, PL
中科院分区：
文献类型：
--
作者：
Borrás, T;Gabelt, BT;Kaufman, PL
背景青光眼是一组常伴有眼压升高的慢性眼病。如果不加以控制，这种情况会导致失明。负责维持房水的眼组织。阻力和正常眼压是小梁网(TM)。腺病毒载体能够在几种啮齿动物中转导TM。由于非人类灵长类动物模型在青光眼研究中的相关性，我们对食蟹猴眼部基因转移进行了研究。方法4只食蟹猴前房注射AdenoGFP：2只猴子接受10(9)PFU，另外2只猴子接受10(7)PFU。一只猴子在7个月的时间里连续四次向同一只眼睛注射(每次注射10(7)pfu)。用标准的临床眼科仪器(裂隙灯生物显微镜、房角镜和眼压计)评价体内基因转移(荧光)和眼压。结果第一次注射较低剂量的病毒后，在活体房角镜下可见明显的TM偏好的基因转移。反式烯的表达持续3-4周，几乎没有临床炎症的迹象。连续3次(每次3~4周)进行基因转移，但在第4次均未成功，并诱发了大量可逆的角膜病变。结论在非人类灵长类动物中，可以无创地监测到TM和角膜的基因转移，使基因转移与生理参数相关联。由于眼部免疫豁免，前房反复给药表达适当基因的腺病毒载体可能对青光眼有治疗潜力。版权所有(C)2001 John Wiley&Sons，Ltd.
Background Glaucoma is a group of chronic eye diseases often associated with an elevated intraocular pressure (IOP). If not controlled, the condition leads to blindness. The eye tissue responsible for maintaining aqueous humor. resistance and thus normal IOP is the trabecular meshwork (TM). Adenoviral vectors are capable of transducing the TM in several rodent species. Because, of the relevance of the non-human primate model in the study of glaucoma, gene transfer to the eyes of cynomolgus monkeys was investigated.Methods Four cynomolgus monkeys were injected with AdenoGFP into the anterior chamber: two monkeys received 10(9) pfu and the other two 10(7) pfu. One monkey received four consecutive injections into the same eye (10(7) pfu in each injection) over a 7-month period. In vivo gene transfer (fluorescence) and IOP were evaluated by standard clinical ophthalmic instruments (slit lamp biomicroscopy, gonioscopy and tonometry). Histopathology and cellular distribution were assessed postmortem.Results The first injection of the lower viral dose resulted in marked TM-preferred gene transfer visible non-invasively by in vivo gonioscopy. The expression of the trans-ene lasted for 3-4 weeks with little or no signs of clinical inflammation. Gene transfer was achieved on three sequential occasions (3-4 weeks each) but failed and induced substantial, albeit reversible, corneal abnormalities on the fourth occasion.Conclusions Gene transfer to the TM and cornea can be monitored noninvasively in non-human primates, allowing correlation of gene transfer with physiological parameters. Because of ocular immune privilege, repeated anterior chamber administrations of adenoviral vectors expressing appropriate genes may have therapeutic potential for glaucoma. Copyright (C) 2001 John Wiley & Sons, Ltd.