Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: Dose-dependent effects on ERG and retinal histology
Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: Dose-dependent effects on ERG and retinal histology
复制标题
DOI：
10.1167/iovs.03-1342
复制
发表时间：
2004-07-01
影响因子：
4.4
通讯作者：
Sieving, PA
中科院分区：
文献类型：
--
作者：
Bush, RA;Lei, B;Sieving, PA
目的：研究在玻璃体内植入释放睫状神经营养因子（CNTF）的包囊细胞技术（ECT）装置后，正常兔的视网膜电图（ERG）和组织学变化。
方法：15只成年新西兰白兔，左眼颞上象限植入分别以22、5或0纳克/天分泌CNTF的ECT装置。低剂量已被证明可在视网膜变性的rcd1犬模型中对光感受器产生显著的挽救作用。右眼未作处理。在植入后5、15和25天进行全视野暗适应和明适应ERG检查及临床观察。在25天评估视杆细胞a波、视杆和视锥细胞b波以及外核层（ONL）形态。
结果：临床检查显示，少数接受CNTF治疗的眼睛有轻微变化，包括在第25天出现玻璃体膜和虹膜血管充血。视网膜外观正常。CNTF对视杆细胞a波或b波无显著影响，尽管在低闪光强度下，接受CNTF治疗的视网膜b波振幅往往较大。在一些闪光强度下，高剂量组眼睛的视锥细胞b波振幅显著降低。由于厚度增加，高剂量组眼睛的ONL面积显著大于对侧视网膜。接受CNTF治疗的视网膜中，ONL细胞大小显著增加，染色密度降低。
结论：通过玻璃体内ECT装置给予在视网膜变性犬模型中可保护光感受器的剂量（5纳克/天）的CNTF，对正常兔视网膜的视杆或视锥细胞ERG功能无不良影响。视锥细胞ERG对抑制更敏感，在低闪光强度下，22纳克/天可使其降低。ONL和光感受器细胞核的剂量相关变化不代表毒性作用，因为在较宽的强度范围内，它们与视杆细胞ERG的缺陷无关。
PURPOSE. ERG and histologic changes were investigated in normal rabbits after intravitreal implantation of encapsulated cell technology (ECT) devices releasing ciliary neurotrophic factor ( CNTF).METHODS. Fifteen adult New Zealand White albino rabbits had ECT devices secreting CNTF at 22, 5, or 0 ng/d implanted in the superior temporal quadrant of the left eye. The low dose has been shown to produce substantial rescue of photoreceptors in the rcd1 canine model of retinal degeneration. Right eyes were untreated. Ganzfeld dark- and light-adapted ERGs and clinical observations were performed at 5, 15, and 25 days after implantation. Rod a-waves and rod and cone b-waves and outer nuclear layer (ONL) morphology were evaluated at 25 days.RESULTS. Clinical examination showed minimal changes in a few CNTF-treated eyes, including vitreous membranes and engorgement of iris vessels at day 25. Retinas appeared normal. CNTF did not significantly affect the rod a- or b-waves, although the b-wave amplitude tended to be larger in CNTF-treated retinas at low flash intensities. The cone b-wave amplitude was significantly reduced in high-dose eyes at some flash intensities. The ONL area in high-dose eyes was significantly greater because of increased thickness than in fellow retinas. ONL cell size was significantly increased, and staining density decreased in CNTF-treated retinas.CONCLUSIONS. CNTF, given by intravitreal ECT device at doses that protect photoreceptors in a canine model of retinal degeneration (5 ng/d), did not adversely affect either rod or cone ERG function of normal rabbit retina. The cone ERG was more sensitive to suppression being reduced, at low flash intensities, by 22 ng/d. Dose-related changes in the ONL and photoreceptor cell nuclei did not represent a toxic effect, because they were not associated with deficits in the rod ERG over a broad range of intensities.