Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

New technologies for developing second generation retinal prostheses

Lab Animal volume 47, pages 71–75 (2018)Cite this article

Abstracts

Inherited or age-dependent retinal dystrophies such as Retinitis pigmentosa (RP) and macular degeneration (MD) are among the most prevalent causes of blindness. Despite enormous efforts, no established pharmacological treatment to prevent or cure photoreceptor degeneration has been identified. Given the relative survival of the inner retina, attempts have been made to restore vision with optogenetics or with retinal neuroprostheses to allow light-dependent stimulation of the inner retinal network. While microelectrode and photovoltaic devices based on inorganic technologies have been proposed and in many cases implanted in RP patients, a new generation of prosthetics based on organic molecules, such as organic photoswitches and conjugated polymers, is demonstrating an unexpected potential for visual rescue and intimate interactions with functioning tissue. Organic devices are starting a new era of tissue electronics, in which light-sensitive molecules and live tissues integrate and tightly interact, producing a new ecosystem of organic prosthetics and intelligent biotic/abiotic interfaces. In addition to the retina, the applications of these interfaces might be extended in the future to other biomedical fields.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Rehabilitating strategies to rescue vision in degenerative blindness.
Fig. 2: Conjugated polymers as light-sensitive neural interfaces.

Similar content being viewed by others

References

  1. Wright, A. F., Chakarova, C. F., Abd El-Aziz, M. M. & Bhattacharya, S. S. Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat. Rev. Genet. 11, 273–284 (2010).

    Article  CAS  PubMed  Google Scholar 

  2. Provis, J. M., Penfold, P. L., Cornish, E. E., Sandercoe, T. M. & Madigan, M. C. Anatomy and development of the macula: specialisation and the vulnerability to macular degeneration. Clin. Exp. Optom 88, 269–281 (2005).

    Article  PubMed  Google Scholar 

  3. Rossi, E. A. & Roorda, A. The relationship between visual resolution and cone spacing in the human fovea. Nat. Neurosci. 13, 156–157 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. Scholl, H. P. et al. Emerging therapies for inherited retinal degeneration. Sci. Transl. Med. 8, 368rv6 (2016).

    Article  PubMed  Google Scholar 

  5. Trapani, I., Banfi, S., Simonelli, F., Surace, E. M. & Auricchio, A. Gene therapy of inherited retinal degenerations: prospects and challenges. Hum. Gene Ther. 26, 193–200 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Maguire, A. M. et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N. Engl. J. Med. 358, 2240–2248 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bennett, J., Chung, D. C. & Maguire, A. Gene delivery to the retina: from mouse to man. Methods Enzymol 507, 255–274 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zarbin, M. Cell-based therapy for degenerative retinal disease. Trends Mol. Med. 22, 115–134 (2016).

    Article  PubMed  Google Scholar 

  9. Garg, A., Yang, J., Lee, W. & Tsang, S. H. Stem cell therapies in retinal disorders. Cells 6, 4 (2017).

    Article  PubMed Central  Google Scholar 

  10. Mandai, M. et al. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. N. Engl. J. Med. 376, 1038–1046 (2017).

    Article  CAS  PubMed  Google Scholar 

  11. Weiland, J. D., Cho, A. K. & Humayun, M. S. Retinal prostheses: current clinical results and future needs. Ophthalmology 118, 2227–2237 (2011).

    Article  PubMed  Google Scholar 

  12. Zrenner, E. Fighting blindness with microelectronics. Sci. Transl. Med. 5, 210ps16 (2013).

    Article  PubMed  Google Scholar 

  13. Ayton, L. N. et al. First-in-human trial of a novel suprachoroidal retinal prosthesis. PLoS One 9, e115239 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Garg, S. J. & Federman, J. Optogenetics, visual prosthesis and electrostimulation for retinal dystrophies. Curr. Opin. Ophthalmol. 24, 407–414 (2013).

    Article  PubMed  Google Scholar 

  15. Luo, Y. H. & da Cruz, L. A review and update on the current status of retinal prostheses (bionic eye). Br. Med. Bull. 109, 31–44 (2014).

    Article  PubMed  Google Scholar 

  16. Humayun, M. S. et al. Interim results from the international trial of Second Sight’s visual prosthesis. Ophthalmology 119, 779–788 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ahnood A et al. Diamond devices for high acuity prosthetic vision. Adv. Biosys. 1600003 (2017).

  18. Zrenner, E. et al. Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc. Biol. Sci. 278, 1489–1497 (2011).

    Article  PubMed  Google Scholar 

  19. Stingl, K. et al. Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc. Biol. Sci. 280, 20130077 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mathieson, K. et al. Photovoltaic Retinal Prosthesis with High Pixel Density. Nat. Photonics 6, 391–397 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mandel, Y. et al. Cortical responses elicited by photovoltaic subretinal prostheses exhibit similarities to visually evoked potentials. Nat. Commun. 4, 1980 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lorach, H. et al. Photovoltaic restoration of sight with high visual acuity. Nat. Med. 21, 476–482 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lanzani, G. Materials for bioelectronics: organic electronics meets biology. Nat. Mater. 13, 775–776 (2014).

    Article  CAS  PubMed  Google Scholar 

  24. Liao, C. et al. Flexible Organic Electronics in Biology: Materials and Devices. Adv. Mater. 27, 7493–7527 (2015).

    Article  CAS  PubMed  Google Scholar 

  25. Antognazza, M. R. et al. Shedding Light on Living Cells. Adv. Mater. 27, 7662–7669 (2015).

    Article  CAS  PubMed  Google Scholar 

  26. Ghezzi, D. et al. A hybrid bioorganic interface for neuronal photoactivation. Nat. Commun. 2, 166 (2011).

    Article  PubMed  Google Scholar 

  27. Feyen, P. et al. Light-evoked hyperpolarization and silencing of neurons by conjugated polymers. Sci. Rep. 6, 22718 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ghezzi, D. et al. A polymer optoelectronic interface restores light sensitivity in blind rat retinas. Nat. Photonics 7, 400–406 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. McGill, T. J., Douglas, R. M., Lund, R. D. & Prusky, G. T. Quantification of spatial vision in the Royal College of Surgeons rat. Invest. Ophthalmol. Vis. Sci. 45, 932–936 (2004).

    Article  PubMed  Google Scholar 

  30. Antognazza, M. R. et al. Characterization of a polymer-based fully organic prosthesis for implantation into the subretinal space of the rat. Adv. Healthc. Mater 5, 2271–2282 (2016).

    Article  CAS  PubMed  Google Scholar 

  31. Maya-Vetencourt, J. F. et al. A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness. Nat. Mater. 16, 681–689 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Palanker, D., Vankov, A., Huie, P. & Baccus, S. Design of a high-resolution optoelectronic retinal prosthesis. J. Neural Eng. 2, S105–S120 (2005).

    Article  PubMed  Google Scholar 

  33. Mosconi, E. et al. Surface Polarization drives photo-induced charge separation at the P3HT/Water interface. ACS Energy Lett 1, 454–463 (2016).

    Article  CAS  Google Scholar 

  34. Ettaiche, M., Deval, E., Cougnon, M., Lazdunski, M. & Voilley, N. Silencing acid-sensing ion channel 1a alters cone-mediated retinal function. J. Neurosci. 26, 5800–5809 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Martino, N. et al. Photothermal cellular stimulation in functional bio-polymer interfaces. Sci. Rep. 5, 8911 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Berdeaux, G. H., Nordmann, J. P., Colin, E. & Arnould, B. Vision-related quality of life in patients suffering from age-related macular degeneration. Am. J. Ophthalmol. 139, 271–279 (2005).

    Article  PubMed  Google Scholar 

  37. Pan, Z. H., Lu, Q., Bi, A., Dizhoor, A. M. & Abrams, G. W. Optogenetic Approaches to Restoring Vision. Annu Rev Vis Sci 1, 185–210 (2015).

    Article  PubMed  Google Scholar 

  38. Duebel, J., Marazova, K. & Sahel, J. A. Optogenetics. Curr. Opin. Ophthalmol. 26, 226–232 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Busskamp, V. et al. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329, 413–417 (2010).

    Article  CAS  PubMed  Google Scholar 

  40. Klapoetke, N. C. et al. Independent optical excitation of distinct neural populations. Nat. Methods 11, 338–346 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chuong, A. S. et al. Noninvasive optical inhibition with a red-shifted microbial rhodopsin. Nat. Neurosci. 17, 1123–1129 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ivanova, E., Hwang, G.-S., Pan, Z.-H. & Troilo, D. Evaluation of AAV-mediated expression of Chop2-GFP in the marmoset retina. Invest. Ophthalmol. Vis. Sci. 51, 5288–5296 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Sengupta, A. et al. Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina. EMBO Mol. Med. 8, 1248–1264 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chaffiol, A. et al. A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina. Mol. Ther. 25, 2546–2560 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bianco, A., Perissinotto, S., Garbugli, M., Lanzani, G. & Bertarelli, C. Control of optical properties through photochromism: a promising approact to photonics. Laser Photonics Rev 5, 711–736 (2011).

    Article  CAS  Google Scholar 

  46. Gorostiza, P. & Isacoff, E. Optical switches and triggers for the manipulation of ion channels and pores. Mol. Biosyst. 3, 686–704 (2007).

    Article  CAS  PubMed  Google Scholar 

  47. Fortin, D. L. et al. Photochemical control of endogenous ion channels and cellular excitability. Nat. Methods 5, 331–338 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Polosukhina, A. et al. Photochemical restoration of visual responses in blind mice. Neuron 75, 271–282 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tochitsky, I. et al. Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells. Neuron 81, 800–813 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Tochitsky, I., Trautman, J., Gallerani, N., Malis, J. G. & Kramer, R. H. Restoring visual function to the blind retina with a potent, safe and long-lasting photoswitch. Sci. Rep. 7, 45487 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Laprell, L. et al. Restoring Light Sensitivity in Blind Retinae Using a Photochromic AMPA Receptor Agonist. ACS Chem. Neurosci. 7, 15–20 (2016).

    Article  CAS  PubMed  Google Scholar 

  52. Colombo, E., Feyen, P., Antognazza, M. R., Lanzani, G. & Benfenati, F. Nanoparticles: A Challenging Vehicle for Neural Stimulation. Front. Neurosci. 10, 105 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Chen, J., Patil, S., Seal, S. & McGinnis, J. F. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat. Nanotechnol. 1, 142–150 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Shapiro, M. G., Homma, K., Villarreal, S., Richter, C. P. & Bezanilla, F. Infrared light excites cells by changing their electrical capacitance. Nat. Commun. 3, 736 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Carvalho-de-Souza, J. L. et al. Photosensitivity of neurons enabled by cell-targeted gold nanoparticles. Neuron 86, 207–217 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sytnyk, M. et al. Cellular interfaces with hydrogen-bonded organic semiconductor hierarchical nanocrystals. Nat. Commun. 8, 91 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work was supported by the EU project FP7-PEOPLE-212-ITN 316832 “OLIMPIA”, Telethon - Italy GGP12033 and GGP14022; Fondazione Cariplo ONIRIS 2013–0738; Compagnia di San Paolo ID 4191; Italian Ministry of Health RF-2013-02358313. The support of Ra.Mo. Foundation (Milano, Italy) and Rare Partners srl (Milano, Italy) is also acknowledged.

Author information

Authors and Affiliations

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

    Fabio Benfenati

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

    Guglielmo Lanzani

Authors
  1. Fabio Benfenati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guglielmo Lanzani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabio Benfenati.

Ethics declarations

Competing interests

The authors declare that they do not have any competing financial interests in relation to the work described.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Benfenati, F., Lanzani, G. New technologies for developing second generation retinal prostheses. Lab Anim 47, 71–75 (2018). https://doi.org/10.1038/s41684-018-0003-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41684-018-0003-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing