Adekunle Adewumi N, Adkins Alice, Wang Wei, Kaplan Henry J, de Castro Juan Fernandez, Lee Sang Joon, Huie Philip, Palanker Daniel, McCall Maureen, Pardue Machelle T
Department of Ophthalmology, Emory University, Atlanta, GA, USA.
Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Atlanta, GA, USA.
Transl Vis Sci Technol. 2015 Aug 14;4(4):5. doi: 10.1167/tvst.4.4.5. eCollection 2015 Aug.
To investigate the integration of subretinal implants containing full-depth perforations of various widths with rat and pig retina across weeks of implantation.
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-μm wide perforations, and active bipolar photovoltaic arrays (bPVA) with 5-μm 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.
Regardless of implant design, retinas of both species showed normal vasculature. In TgP23H-1 retinas implanted with 10-μm 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-μm perforated IPAs. TgP23H-1 retinas with bPVAs showed similar INL migration to retinas with 5-μm 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.
In retinas with photoreceptor degeneration, solid implants, or those with 5-μm perforations lead to the best biocompatibility.
研究不同宽度全层穿孔的视网膜下植入物在大鼠和猪视网膜中植入数周后的整合情况。
在转基因P23H视紫红质1型（TgP23H-1）大鼠和野生型（WT）猪中，我们检查了四种视网膜下植入物设计：实心无活性聚合物阵列（IPA）、具有5或10μm宽穿孔的IPA以及具有5μm穿孔的有源双极光伏阵列（bPVA）。我们通过大鼠的外部入路或猪的玻璃体视网膜入路将植入物手术放置到视网膜下间隙。使用光学相干断层扫描验证植入物在视网膜下间隙的放置，并通过荧光素血管造影表征视网膜灌注。在植入后8周或16周（wpi）处死大鼠，在2、4或8 wpi处死猪，并在光镜水平评估视网膜。
无论植入物设计如何，两种物种的视网膜均显示正常血管系统。在植入10μm穿孔IPA的TgP23H-1视网膜中，内核层（INL）细胞在8 wpi时通过穿孔迁移，导致到16 wpi时INL显著变薄。此外，与实心或5μm穿孔IPA的视网膜相比，这些视网膜显示出更多的假玫瑰花结形成和纤维化。带有bPVA的TgP23H-1视网膜显示出与5μm穿孔IPA的视网膜相似的INL迁移，纤维化和玫瑰花结形成较少。带有穿孔IPA的WT猪视网膜维持了光感受器，未显示迁移，假玫瑰花结形成较少，但与植入的TgP23H-1大鼠视网膜相比纤维化更多。
在有光感受器变性的视网膜中，实心植入物或具有5μm穿孔的植入物具有最佳的生物相容性。
