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A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

Nature Materials volume 16, pages 681–689 (2017)Cite this article

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Abstract

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of retinitis pigmentosa. Electrophysiological and behavioural analyses reveal a prosthesis-dependent recovery of light sensitivity and visual acuity that persists up to 6–10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness.

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Figure 1: The organic prosthesis and the subretinal implant.
Figure 2: Pupillary reflex and topographic specificity of the prosthesis signal at the cortical level.
Figure 3: Electrophysiological assessment of cortical visual responses in response to flash and patterned illumination.
Figure 4: Behavioural evaluation of visual functions.
Figure 5: Basal metabolic activity in V1.
Figure 6: Characterization of the prosthesis after long-term implantation.

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Acknowledgements

The authors thank M. M. La Vail (Beckman Vision Center, University of California San Francisco, California) for providing non-dystrophic RCS-rdy+ and dystrophic RCS rats; G. Vijfvinkel (Oftavinci BV, Geervliet, The Netherlands) for manufacturing specific surgical tools for implantation; L. Criante and S. Perissinotto for help at the laser micro-machining facility; M. Bramini and F. D. Fonzo for help in scanning electron microscopy; A. Russo, C. Orsini, F. Canu, I. Dall’Orto, A. Mehilli and D. Moruzzo for technical assistance. The work was supported by the EU project FP7-PEOPLE-212-ITN 316832 ‘OLIMPIA’ (to F.B. and G.L.); Telethon—Italy (grants GGP12033 to G.L., F.B. and S.B. and GGP14022 to G.P. and F.B.); Fondazione Cariplo (project ONIRIS 2013–0738 to MRA, G.F. and D.G.); Compagnia di San Paolo (project ID 4191 to D.G. and F.B.), the Italian Ministry of Health (project RF-2013-02358313 to G.P., G.L. and F.B.) and Istituto Italiano di Tecnologia (pre-startup project to G.L. and F.B.). The support of Ra.Mo. Foundation (Milano, Italy) and Rare Partners srl (Milano, Italy) is also acknowledged.

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Author notes

  1. Diego Ghezzi

    Present address: Present address: Center for Neuroprosthetics, Interfaculty Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.,

  2. José Fernando Maya-Vetencourt and Diego Ghezzi: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, 16132 Genoa, Italy

    José Fernando Maya-Vetencourt, Diego Ghezzi, Elisabetta Colombo, Paul Feyen, Dmytro Shmal & Fabio Benfenati

  2. Center for Nano Science and Technology, Istituto Italiano di Tecnologia, 20133 Milan, Italy

    Maria Rosa Antognazza, Andrea Desii & Guglielmo Lanzani

  3. Ophthalmology Department, Sacro Cuore Hospital—Don Calabria, 37024 Negrar, Italy

    Maurizio Mete & Grazia Pertile

  4. Department of Health Science, Nuclear Medicine, University of Genoa, 16132 Genoa, Italy

    Ambra Buschiazzo, Flavia Ticconi & Gianmario Sambuceti

  5. Department of Biotechnology and Applied Clinical Science, University of L’Aquila, 67100, Italy

    Mattia Di Paolo, Stefano Di Marco, Rita Maccarone & Silvia Bisti

  6. Animal Facility, National Institute Cancer Research, IRCCS AOU San Martino-IST, 16132 Genoa, Italy

    Laura Emionite

  7. Institute of Molecular Bio-imaging and Physiology (IBFM), CNR, 16163 Milan (GE section), Italy

    Cecilia Marini

  8. Silk Division, Innovhub-SSI, 20133 Milan, Italy

    Ilaria Donelli & Giuliano Freddi

  9. Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy

    Fabio Benfenati

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  1. José Fernando Maya-Vetencourt
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Contributions

J.F.M.-V. and D.G. contributed equally to this work. J.F.M.-V. carried out in vivo electrophysiology experiments, behavioural analysis, and assisted in the PET trials; D.G. executed behavioural experiments, the PLR analysis, and preliminary electrophysiology; M.R.A. and A.D. fabricated and characterized the implants under the supervision of G.L.; I.D. and G.F. purified the silk protein used for the implants; M.M. and G.P. performed OCT analysis, developed and executed the chirurgical subretinal implantation; P.F. and E.C. carried out behavioural experiments; E.C. carried out the post-mortem studies on the devices; A.B., F.T., L.E., D.S. and C.M. executed PET experiments under the supervision of G.S.; M.D.P., S.D.M. and R.M. performed histological analysis under the supervision of S.B.; F.B. and G.L., conceived, supervised, and financed the project. J.F.M.-V., G.L. and F.B. wrote the manuscript. All authors discussed the experimental results and commented on the manuscript.

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Correspondence to Fabio Benfenati.

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Maya-Vetencourt, J., Ghezzi, D., Antognazza, M. et al. A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness. Nature Mater 16, 681–689 (2017). https://doi.org/10.1038/nmat4874

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