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K.L. Kohler, H. Sachs, E. Zrenner, H. Richter; Tissue Reaction and Biocompatibility Following Long-Term Implantation of Electrical Devices into the Subretinal Space of Cats and Pigs . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5071.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the status of the retina and RPE covering the inner and outer surface of microphotodiode arrays (MPDAs) implanted into the subretinal space. Methods: Following local retinal detachment and retinotomy, MPDAs were inserted into the subretinal space. After an implantation period of up to 15 months in cats and 29 months in Yucatan minipigs, eyes were enucleated and processed for histology. The implant was removed, serial sections were cut along the implantation area, and cell numbers and thickness of the retinal layers were quantified. Immunohistochemistry was used to monitor changes in the network of distinct neuronal cell types and in glia reactivity. Some implants were left in situ and processed as a combined tissue/device preparation. Results: Due to the blocked nutrition of the outer retina by the subretinal implant most of the photoreceptors overlying the implant degenerated. However, 1-3 rows of ONL-cells were still present more than 2 years after implantation in pigs and to a lesser extend also in cats. The preservation of the inner retina varies but was in general much better in pigs than in cats. Cell loss and hyperplasia of Muller glia was minimized in those areas where at least one row of ONL-cells remained. Inner and outer surfaces of all implants were covered with a fibrous membrane. This membrane was less than 10 µm thick in pigs. It occasionally accumulated to a coating thickness of several cell layers in cats and in animals with a post-operative edema or a delayed adherence of the retina to the surface of the implant. A massive fibrosis was accompanied by strong glia reactions and disturbances in the retinal architecture. The majority of the implanted animals developed only minimal fibrosis and mild fibrosis was always correlated with residues of ONL-cells. The neuronal network of horizontal, amacrine, and ganglion cells was well preserved and without substantial deficits in these retinas as shown by morphometry and immunohistochemistry. Disruption of the RPE and opening of the Blood-Retina-Barrier was closed by cell proliferation and formation of a fibrous scare. Conclusions: Our subretinal implants were well tolerated by the retina and RPE over more than two years in situ. The preservation of the inner retinal network indicates that signal procession is still possible after that period. A quick and proper attachment of the retina to the surface of the implant after surgery seems to be a crucial prerequisite to minimize the formation of fibrous membranes.
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