Tao Weng, Wen Rong, Goddard Moses B, Sherman Sandy D, O'Rourke Pam J, Stabila Paul F, Bell William J, Dean Brenda J, Kauper Konrad A, Budz Veronica A, Tsiaras William G, Acland Gregory M, Pearce-Kelling Sue, Laties Alan M, Aguirre Gustavo D
Neurotech USA, Lincoln, Rhode Island 02865, USA.
Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3292-8.
The objective of the present study was to evaluate the therapeutic efficacy of ciliary neurotrophic factor (CNTF) delivered through encapsulated cells directly into the vitreous of the eye in an rcd1 canine model of retinitis pigmentosa. The dose-range effect of the treatment was also investigated.
Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell-containing capsules were then surgically implanted into the vitreous of one eye of rcd1 dogs at 7 weeks of age, when retinal degeneration is in progress but not complete. The contralateral eyes were not treated. The capsules remained in the eyes for 7 weeks. At the end of the studies, the capsules were explanted, and CNTF output and cell viability were evaluated. The eyes were processed for histologic evaluation.
In each animal, the number of rows of photoreceptor nuclei in the outer nuclear layer (ONL) was significantly higher in the eye that received a CNTF-secreting implant than in the untreated contralateral eye. No adverse effects were observed on the retina in the treated eyes. The explanted capsules produced a low level of CNTF. The cells in the capsules remained viable and densely distributed throughout.
CNTF delivered through encapsulated cells directly into the vitreous of the eye protects photoreceptors in the PDE6B-deficient rcd1 canine model. Furthermore, sparing of photoreceptors appeared dose-dependent with minimum protection observed at CNTF doses of 0.2 to 1.0 ng/d. Incrementally greater protection was achieved at higher doses. The surgically implanted, cell-containing capsules were well tolerated, and the cells within the capsule remained viable for the 7-week implantation interval. These results suggest that encapsulated cell therapy may provide a safe and effective strategy for treating retinal disorders in humans.
本研究的目的是评估在视网膜色素变性的rcd1犬模型中，通过封装细胞直接将睫状神经营养因子（CNTF）注入眼玻璃体内的治疗效果。同时还研究了该治疗的剂量范围效应。
将聚合物膜胶囊（长1.0厘米，直径1.0毫米）装载经基因工程改造以分泌CNTF的哺乳动物细胞。然后在7周龄的rcd1犬处于视网膜变性进行但未完成时，通过手术将含细胞的胶囊植入一只眼睛的玻璃体内。对侧眼睛不进行治疗。胶囊在眼中保留7周。在研究结束时，取出胶囊，评估CNTF输出和细胞活力。对眼睛进行组织学评估。
在每只动物中，接受分泌CNTF植入物的眼睛的外核层（ONL）中光感受器细胞核的行数明显高于未治疗的对侧眼睛。在治疗的眼睛中未观察到对视网膜的不良反应。取出的胶囊产生低水平的CNTF。胶囊中的细胞保持存活并密集分布。
通过封装细胞直接将CNTF注入眼玻璃体内可保护PDE6B缺陷的rcd1犬模型中的光感受器。此外，光感受器的保留似乎呈剂量依赖性，在CNTF剂量为0.2至1.0纳克/天时观察到最小保护作用。在更高剂量下可实现逐渐增强的保护。手术植入的含细胞胶囊耐受性良好，胶囊内的细胞在7周的植入间隔内保持存活。这些结果表明，封装细胞疗法可能为治疗人类视网膜疾病提供一种安全有效的策略。
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