Integration of Perforated Subretinal Prostheses With Retinal Tissue

Integration of Perforated Subretinal Prostheses With Retinal Tissue
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DOI:
10.1167/tvst.4.4.5
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发表时间:
2015-07-01
影响因子:
3
通讯作者:
Pardue, Machelle T.
Pardue, Machelle T.
中科院分区:
医学3区
文献类型:
--
作者:
Adekunle, Adewumi N.;Adkins, Alice;Pardue, Machelle T.

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目的:研究不同宽度的全深度穿孔视网膜下植入物与大鼠和猪视网膜在植入数周后的融合情况。方法:在转基因P23H视紫红质系1 (TgP23H-1)大鼠和野生型猪中,我们研究了四种视网膜下植入物设计:固体无活性聚合物阵列(IPA), 5或10 μ m宽穿孔的IPA,以及5 μ m穿孔的有源双极光伏阵列(bPVA)。我们通过手术将植入物置入视网膜下空间,在大鼠中采用外入路,在猪中采用玻璃体视网膜入路。通过光学相干断层扫描验证植入物在视网膜下空间的放置,并用荧光素血管造影表征视网膜灌注。大鼠在植入后8周或16周,猪在植入后2周、4周或8周处死,在光镜下评估视网膜。结果:无论植入体设计如何,两种动物的视网膜血管系统均正常。在植入10 μ m穿孔IPAs的TgP23H-1视网膜中,内核层(INL)细胞通过穿孔迁移了8 wpi,导致INL明显变薄16 wpi。此外,与实性或5 μ m穿孔IPAs的视网膜相比,这些视网膜显示出更大的伪玫瑰结形成和纤维化。具有bpva的TgP23H-1视网膜与具有5 μ m穿孔IPAs的视网膜具有相似的INL迁移,纤维化和玫瑰花结形成较少。与植入TgP23H-1的大鼠视网膜相比,IPAs穿孔的WT猪视网膜维持了光感受器,没有迁移,假性玫瑰花结形成较少,但纤维化较多。结论:在光感受器变性视网膜中,实体植入物或有5 μ m穿孔的视网膜具有最佳的生物相容性。
Purpose: To investigate the integration of subretinal implants containing full-depth perforations of various widths with rat and pig retina across weeks of implantation.Methods: In transgenic P23H rhodopsin line 1 (TgP23H-1) rats and wild-type (WT) pigs, we examined four subretinal implant designs: solid inactive polymer arrays (IPA), IPAs with 5- or 10-mu m wide perforations, and active bipolar photovoltaic arrays (bPVA) with 5-mu m perforations. We surgically placed the implants into the subretinal space using an external approach in rats or a vitreoretinal approach in pigs. Implant placement in the subretinal space was verified with optical coherence tomography and retinal perfusion was characterized with fluorescein angiography. Rats were sacrificed 8 or 16 weeks post-implantation (wpi) and pigs 2, 4, or 8 wpi, and retinas evaluated at the light microscopic level.Results: Regardless of implant design, retinas of both species showed normal vasculature. In TgP23H-1 retinas implanted with 10-mu m perforated IPAs, inner nuclear layer (INL) cells migrated through the perforations by 8 wpi, resulting in significant INL thinning by 16 wpi. Additionally, these retinas showed greater pseudo-rosette formation and fibrosis compared with retinas with solid or 5-mu m perforated IPAs. TgP23H-1 retinas with bPVAs showed similar INL migration to retinas with 5-mu m perforated IPAs, with less fibrosis and rosette formation. WT pig retina with perforated IPAs maintained photoreceptors, showed no migration, and less pseudo-rosette formation, but more fibrosis compared with implanted TgP23H-1 rat retinas.Conclusions: In retinas with photoreceptor degeneration, solid implants, or those with 5-mu m perforations lead to the best biocompatibility.