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


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.


  1. 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).

    CAS  Google Scholar 

  2. 2

    Smith, A. J., Bainbridge, J. W. & Ali, R. R. Gene supplementation therapy for recessive forms of inherited retinal dystrophies. Gene Ther. 19, 154–161 (2012).

    CAS  Google Scholar 

  3. 3

    Hartong, D. T., Berson, E. L. & Dryja, T. P. Retinitis pigmentosa. Lancet 368, 1795–1809 (2006).

    CAS  Google Scholar 

  4. 4

    Frasson, M. et al. Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse. Nat. Med. 5, 1183–1187 (1999).

    CAS  Google Scholar 

  5. 5

    Leveillard, T. & Sahel, J. A. Rod-derived cone viability factor for treating blinding diseases: from clinic to redox signaling. Sci. Transl. Med. 2, 26ps16 (2010).

    Google Scholar 

  6. 6

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

    CAS  Google Scholar 

  7. 7

    Pearson, R. A. et al. Restoration of vision after transplantation of photoreceptors. Nature 485, 99–103 (2012).

    CAS  Google Scholar 

  8. 8

    Barber, A. C. et al. Repair of the degenerate retina by photoreceptor transplantation. Proc. Natl Acad. Sci. USA 110, 354–359 (2013).

    CAS  Google Scholar 

  9. 9

    Gerding, H., Benner, F. P. & Taneri, S. Experimental implantation of epiretinal retina implants (EPI-RET) with an IOL-type receiver unit. J. Neural Eng. 4, S38–S49 (2007).

    CAS  Google Scholar 

  10. 10

    Walter, P. et al. Cortical activation via an implanted wireless retinal prosthesis. Invest. Ophthalmol. Vis. Sci. 46, 1780–1785 (2005).

    Google Scholar 

  11. 11

    DeMarco, P. J. Jr et al. Stimulation via a subretinally placed prosthetic elicits central activity and induces a trophic effect on visual responses. Invest. Ophthalmol. Vis. Sci. 48, 916–926 (2007).

    Google Scholar 

  12. 12

    Mathieson, K. et al. Photovoltaic retinal prosthesis with high pixel density. Nat. Photon. 6, 391–397 (2012).

    CAS  Google Scholar 

  13. 13

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

    Google Scholar 

  14. 14

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

    CAS  Google Scholar 

  15. 15

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

    Google Scholar 

  16. 16

    Yanai, D. et al. Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am. J. Ophthalmol. 143, 820–827 (2007).

    Google Scholar 

  17. 17

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

    Google Scholar 

  18. 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).

    Google Scholar 

  19. 19

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

    Google Scholar 

  20. 20

    Zrenner, E. Will retinal implants restore vision? Science 295, 1022–1025 (2002).

    CAS  Google Scholar 

  21. 21

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

    Google Scholar 

  22. 22

    Laube, T. et al. Development of surgical techniques for implantation of a wireless intraocular epiretinal retina implant in Gottingen minipigs. Graefes. Arch. Clin. Exp. Ophthalmol. 250, 51–59 (2012).

    Google Scholar 

  23. 23

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

    Google Scholar 

  24. 24

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

    CAS  Google Scholar 

  25. 25

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

    CAS  Google Scholar 

  26. 26

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

    CAS  Google Scholar 

  27. 27

    Gal, A. et al. Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat. Genet. 26, 270–271 (2000).

    CAS  Google Scholar 

  28. 28

    Di Paolo, M. et al. Inflammatory and morphological characterization of a foreign body retinal response. Eur. J. Neurodegener. Dis. 4, 23–28 (2015).

    Google Scholar 

  29. 29

    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).

    CAS  Google Scholar 

  30. 30

    Gias, C. et al. Degeneration of cortical function in the Royal College of Surgeons rat. Vision Res. 51, 2176–2185 (2011).

    Google Scholar 

  31. 31

    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).

    Google Scholar 

  32. 32

    Lucas, R. J. et al. Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science 299, 245–247 (2003).

    CAS  Google Scholar 

  33. 33

    Hubener, M. Mouse visual cortex. Curr. Opin. Neurobiol. 13, 413–420 (2003).

    CAS  Google Scholar 

  34. 34

    Morimoto, T. et al. Transcorneal electrical stimulation promotes the survival of photoreceptors and preserves retinal function in royal college of surgeons rats. Invest. Ophthalmol. Vis. Sci. 48, 4725–4732 (2007).

    Google Scholar 

  35. 35

    Ni, Y. Q., Gan, D. K., Xu, H. D., Xu, G. Z. & Da, C. D. Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration. Exp. Neurol. 219, 439–452 (2009).

    Google Scholar 

  36. 36

    Zhou, W. T. et al. Electrical stimulation ameliorates light-induced photoreceptor degeneration in vitro via suppressing the proinflammatory effect of microglia and enhancing the neurotrophic potential of Müller cells. Exp. Neurol. 238, 192–208 (2012).

    CAS  Google Scholar 

  37. 37

    Maya-Vetencourt, J. F. et al. The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science 320, 385–388 (2008).

    CAS  Google Scholar 

  38. 38

    Maya-Vetencourt, J. F. Experience-dependent expression of NPAS4 regulates plasticity in adult visual cortex. J. Physiol. 590, 4777–4787 (2012).

    CAS  Google Scholar 

  39. 39

    LaVail, M. M. & Battelle, B. A. Influence of eye pigmentation and light deprivation on inherited retinal dystrophy in the rat. Exp. Eye Res. 21, 167–192 (1975).

    CAS  Google Scholar 

  40. 40

    Lennerstrand, G. Delayed visual evoked cortical potentials in retinal disease. Acta Ophthalmol. (Copenh) 60, 497–504 (1982).

    CAS  Google Scholar 

  41. 41

    Bourin, M. & Hascoet, M. The mouse light/dark box test. Eur. J. Pharmacol. 463, 55–65 (2003).

    CAS  Google Scholar 

  42. 42

    Phelps, M. E. Positron computed tomography studies of cerebral glucose metabolism in man: theory and application in nuclear medicine. Semin. Nucl. Med. 11, 32–49 (1981).

    CAS  Google Scholar 

  43. 43

    Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates Vol. 6 (Elsevier, 2007).

    Google Scholar 

  44. 44

    Hustinx, R., Smith, R. J., Benard, F., Bhatnagar, A. & Alavi, A. Can the standardized uptake value characterize primary brain tumors on FDG-PET? Eur. J. Nucl. Med. 26, 1501–1509 (1999).

    CAS  Google Scholar 

  45. 45

    Vaquero Morata, S. et al. Organic semiconducting polymers for in vitro cell growth and photostimulation. J. Mater. Chem. B 4, 5272–5283 (2016).

    Google Scholar 

  46. 46

    Tsoi, W. C. et al. The nature of in-plane skeleton Raman modes of P3HT and their correlation to the degree of molecular order in P3HT:PCBM blend thin films. J. Am. Chem. Soc. 133, 9834–9843 (2011).

    CAS  Google Scholar 

  47. 47

    Stavytska-Barba, M. & Myers Kelley, A. Surface-enhanced Raman study of the interaction of PEDOT:PSS with plasmonically active nanoparticles. J. Phys. Chem. C 114, 6822–6830 (2010).

    CAS  Google Scholar 

  48. 48

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

    CAS  Google Scholar 

  49. 49

    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).

    CAS  Google Scholar 

  50. 50

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

    CAS  Google Scholar 

  51. 51

    Stavrinidou, E. et al. Direct measurement of ion mobility in a conducting polymer. Adv. Mater. 25, 4488–4493 (2013).

    CAS  Google Scholar 

  52. 52

    Pizzorusso, T. et al. Structural and functional recovery from early monocular deprivation in adult rats. Proc. Natl Acad. Sci. USA 103, 8517–8522 (2006).

    CAS  Google Scholar 

  53. 53

    Huang, Z. J. et al. BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98, 739–755 (1999).

    CAS  Google Scholar 

  54. 54

    Marini, C. et al. Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer. Cell Cycle 12, 3490–3499 (2013).

    CAS  Google Scholar 

Download references


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.

Author information




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.

Corresponding author

Correspondence to Fabio Benfenati.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 11119 kb)

Supplementary Information

Supplementary movie 1 (MP4 1748 kb)

Supplementary Information

Supplementary movie 2 (MP4 5580 kb)

Supplementary Information

Supplementary movie 3 (MP4 8991 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Further reading


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