Adewumi N Adekunle1, Alice Adkins2, Wei Wang3, Henry J Kaplan3, Juan Fernandez de Castro3, Sang Joon Lee4, Philip Huie5, Daniel Palanker5, Maureen McCall6, Machelle T Pardue7. 1. Department of Ophthalmology, Emory University, Atlanta, GA, USA. 2. Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Atlanta, GA, USA. 3. Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA. 4. Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Ophthalmology, Kosin University, Busan, Korea. 5. Department of Ophthalmology, Stanford University, Palo Alto, CA, USA ; Hansen Experimental Physics Laboratory, Stanford University, Palo Alto, CA, USA. 6. Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA. 7. Department of Ophthalmology, Emory University, Atlanta, GA, USA ; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Atlanta, GA, USA.
Abstract
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-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. RESULTS: 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. CONCLUSIONS: In retinas with photoreceptor degeneration, solid implants, or those with 5-μm perforations lead to the best biocompatibility.
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-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. RESULTS: 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. CONCLUSIONS: In retinas with photoreceptor degeneration, solid implants, or those with 5-μm perforations lead to the best biocompatibility.
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