Integration of Perforated Subretinal Prostheses With Retinal Tissue.
OBJECTIVE
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.
Department of Ophthalmology, Emory University, Atlanta, GA, USA.
Adewumi N
AN
Adekunle
Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Atlanta, GA, USA.
Alice
A
Adkins
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA.
Wei
W
Wang
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA.
Henry J
HJ
Kaplan
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA.
Juan Fernandez
JF
de Castro
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Ophthalmology, Kosin University, Busan, Korea.
Sang Joon
SJ
Lee
Department of Ophthalmology, Stanford University, Palo Alto, CA, USA ; Hansen Experimental Physics Laboratory, Stanford University, Palo Alto, CA, USA.
Philip
P
Huie
Department of Ophthalmology, Stanford University, Palo Alto, CA, USA ; Hansen Experimental Physics Laboratory, Stanford University, Palo Alto, CA, USA.
Daniel
D
Palanker
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA.
Maureen
M
McCall
Department of Ophthalmology, Emory University, Atlanta, GA, USA ; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Atlanta, GA, USA.
Machelle T
MT
Pardue
biocompatibility; migration; prosthetic; retina; retinitis pigmentosa