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P. Huie, I. Chan, A. Vankov, A. Butterwick, M. Marmor, M.S. Blumenkranz, B.W. Jones, D. Palanker; Retinal Migration Into 3–Dimensional Subretinal Prosthetic Implants . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3215.
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© ARVO (1962-2015); The Authors (2016-present)
High spatial resolution of retinal stimulation requires close proximity of electrodes to the target cells. Placement of flat prosthetic implants epiretinally or subretinally typically results in a separation from target cells by several tens of µm. Much closer proximity would be achieved if one could promote retinal migration into the interstices of subretinal implants that have cavities or closely spaced pillars facing the retinal tissue.
3–dimensional arrays having either chambers with apertures of 10–15 µm in width or pillars of 10 µm in diameter were fabricated lithographically using UV–sensitive polymers. The depth of the chambers and the height of the pillars could be adjusted and was kept within a range of 40 – 70 µm. A special surgical tool has been developed for safe insertion of the implant into the subretinal space through a scleral incision. Implantations into the RCS rats were performed after the complete degeneration of the photoreceptors (45–65 days of age). Histological analysis has been performed in 18 rats 2 and 6 weeks post–operatively.
Intimate proximity between stimulation sites and cells in the inner nuclear layer has been achieved using both the chamber and pillar arrays. Complete and non–traumatic penetration of the pillars into the inner nuclear layer has been observed with a pixel density up to 2500 pix/mm2 (center–to–center pillar spacing of 20 µm).
A wet implantation technique that involves injection of liquid into the subretinal space prior to insertion of the implant was found to be less traumatic than a dry technique. With wet implantation the retina tolerated the implant very well, including rapid (72 hours) migration of retinal cells into the implant and no fibrosis. Computational molecular phenotyping has shown that bipolar and amacrine cells in proximity to the implant maintain their normal molecular signatures, indicating normal metabolic status. Traumatic implantations (mostly dry) led to retinal edema and a fibrotic seal within 6 weeks, especially around the flat parts of the implant.
Three–dimensional subretinal implants with pillars or cavities can take advantage of the intrinsic plasticity of the retina since neurite extension and migration bring retinal cellular components into close proximity of electrodes. This will allow a higher efficacy of stimulation. Atraumatic insertion of the implant is very important for assuring integration of the device with the retina and for avoiding a fibrotic seal.
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