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Subretinal implantation and testing of polyimide film electrodes in cats

  • Helmut G. Sachs
  • Thomas Schanze
  • Marcus Wilms
  • Andreas Rentzos
  • Ursula Brunner
  • Florian Gekeler
  • Lutz Hesse
Laboratory Investigation

Abstract

Background

Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. One concept under investigation is an electronic subretinal prosthesis to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa.

Methods

In the subretinal prosthesis design concept, an array of stimulation electrodes is placed in the subretinal space. To test the feasibility of the concept and to determine basic stimulation parameters, wire-bound stimulation devices were used in acute trials for up to 12 h in three eyes in anaesthetised cats. These wire-bound stimulation elements were based on strips of polyimide film. The film strips were introduced through a sclerostomy into the vitreous cavity and via a retinotomy into the subretinal space during a modification of the standard three-port vitrectomy procedure. On entry through the retinotomy, the film was advanced mechanically to the desired position in the area centralis. Perfluorocarbon liquid (PFCL) was used to establish close contact between the electrode array and the outer retina. Stimulation was performed with computer-generated sequences of current waveforms in acute trials immediately after surgical implantation of the stimulation film. Cortical recordings in the primary visual cortex were performed with electrodes placed in locations corresponding to the retinal stimulus site.

Results

All three implantations were carried out successfully with the stimulation array implanted beneath the outer retina of the area centralis of the operated eye. The retina was attached over the stimulation array in all cases. No cortical responses were recorded in one of the stimulation sessions. The results from another session revealed clear intracortical responses to subretinal stimulation with polyimide films. Following single-site retina stimulation, the estimates of spatial cortical resolution and temporal resolution were approximately 1 mm and 20–50 ms, respectively.

Discussion

Our results indicate that focal subretinal stimulation evokes localised spatio-temporal distribution of cortical responses. These findings offer hope that coarse restoration of vision may be feasible by subretinal electrical stimulation.

Keywords

Retinitis Pigmentosa Cortical Response Vitreous Cavity Polyimide Film Subretinal Space 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors gratefully acknowledge the excellent technical assistance of W. Gerber, M. Grosch, C. Csellner, and P. Muth, Applied Physics-NeuroPhysics Group, Department of Physics, Philipps University Marburg, Germany. We thank our colleagues in the MPDA Team for their ongoing cooperation, especially W. Nisch and H. Sailer from the Natural Science Institute (NMI) in Reutlingen, Germany for providing us with the stimulation film electrodes. Special thanks to R. Eckhorn, V.-P. Gabel, and E. Zrenner for valuable discussions and encouragement. Supported by grants from the German Federal Ministry of Education, Science, Research, and Technology (BMBF) 01 KP 0006 and 01 KP 0012.

References

  1. 1.
    Bak M, Girvin JP, Hambrecht FT, Kufta CV, Loeb GE, Schmidt EM (1990) Visual sensations produced by intracortical microstimulation of the human occipital cortex. Med Biol Eng Comput 28:257–259PubMedGoogle Scholar
  2. 2.
    Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willet W (1993) Vitamin A supplementation for retinitis pigmentosa. Arch Ophthalmol 111:1456–1459PubMedGoogle Scholar
  3. 3.
    Brindley GS (1973) Sensory effects of electrical stimulation of the visual and paravisual cortex in man. In: Jung R (ed) Handbook of sensory physiology, vol. 7, sect 3B. Springer, Berlin Heidelberg New York, pp 583–594Google Scholar
  4. 4.
    Brindley GS, Lewin WS (1968) The sensations produced by electrical stimulation of the visual cortex. J Physiol (Lond) 196:479–493Google Scholar
  5. 5.
    Chow AY, Chow VY (1997) Subretinal electrical stimulation of the rabbit retina. Neurosci Lett 225:13–16CrossRefPubMedGoogle Scholar
  6. 6.
    Chow AY, Pardue MT, Chow VY, Peyman GA, Liang C, Perlman JI, Peachy NS (2001) Implantation of silicon chip microphotodiode arrays into the cat subretinal space. IEEE Trans Neural Syst Rehabil Eng 9:86–95CrossRefPubMedGoogle Scholar
  7. 7.
    Dobelle WH (2000) Artificial vision for the blind by connecting a television camera to the visual cortex. ASAIO J 46:3–9CrossRefPubMedGoogle Scholar
  8. 8.
    Dobelle WH, Mladejovsky MG, Girvin JP (1974) Artificial vision for the blind: electrical stimulation of visual cortex offers hope for a functional prosthesis. Science 183:440–444PubMedGoogle Scholar
  9. 9.
    Dobelle WH, Mladejovsky MG, Evans JK, Roberts TS, Girvin JP (1976) ‘Braille’ reading by a blind volunteer by visual cortex stimulation. Nature 259:111–112PubMedGoogle Scholar
  10. 10.
    Eckhorn R, Thomas U (1993) A new method for the insertion of multiple microprobes into neural and muscular tissue, including fiber electrodes, fine wires, needles and microsensors. J Neurosci Methods 49:175–179CrossRefPubMedGoogle Scholar
  11. 11.
    Eckmiller R (1995) Towards retina implants for improvement of vision in humans with retinitis pigmentosa—challenges and first results. In: Proc WCNN 95, Washington DC. INNS Press, New Jersey, pp 228–233Google Scholar
  12. 12.
    Eckmiller R (1997) Learning retina implants with epiretinal contacts. Ophthalmic Res 29:281–289PubMedGoogle Scholar
  13. 13.
    Eckmiller R, Eckhorn R et al (1994) Final report of the feasibility study for a neurotechnology program. In: Eckmiller R (ed) Neurotechnology report. BMBF, Bonn, GermanyGoogle Scholar
  14. 14.
    Girvin J (1988) Current status of artificial vision by electrocortical stimulation. Can J Neurol Sci 15:58–62PubMedGoogle Scholar
  15. 15.
    Haemmerle H, Kobuch K, Kohler K, Nisch W, Sachs H, Stelzle M (2002) Biostability of micro-photodiode arrays for subretinal implantation. Biomaterials 23:797–804CrossRefPubMedGoogle Scholar
  16. 16.
    Hesse L, Schanze T, Wilms M, Eger M (2000) Implantation of retina stimulation electrodes and recording of electrical stimulation responses in the visual cortex of the cat. Graefes Arch Clin Exp Ophthalmol 238:840–845CrossRefPubMedGoogle Scholar
  17. 17.
    Humayun M, Propst R, de Juan E, McCormick K, Hickingbotham D (1994) Bipolar surface electrical stimulation of the vertebrate retina. Arch Ophthalmol 112:110–116PubMedGoogle Scholar
  18. 18.
    Humayun MS, de Juan E, Dagnelie G, Greenberg RJ, Propst RH, Phillips DH (1996) Visual perception elicited by electrical stimulation of retina in blind humans. Arch Ophthalmol 114:40–46PubMedGoogle Scholar
  19. 19.
    Humayun MS, Prince M, de Juan E Jr, Barron Y, Moskowitz M, Klock IB, Milam AH (1999) Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa. Invest Ophthalmol Vis Sci 40:143–148PubMedGoogle Scholar
  20. 20.
    Humayun MS, Weiland JD, Fujii GY, Greenberg R, Williamson R, Little J, Mech B, Cimmarusti V, Van Boemel G, Dagnelie G, de Juan E Jr (2003) Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vis Res 43:2573–2581CrossRefPubMedGoogle Scholar
  21. 21.
    Ito N, Shirahata A, Yagi T, Matsushima T, Kawase K, Watanabe M, Uchikawa Y (1997) Development of artificial retina using cultured neural cells and photoelectric device: a study on electric current with membrane model. Proceedings of The 4th International Conference on Neural Information Processing (ICONIP ‘97), pp 124–127Google Scholar
  22. 22.
    Krumpazsky HG, Klauss V (1996) Epidemiology of blindness and eye disease. Ophthalmologica 210:1–84PubMedGoogle Scholar
  23. 23.
    Normann RA, Maynard EM, Rousche PJ, Warren DJ (1999) A neural interface for a cortical vision prosthesis. Vis Res 39:2577–2587CrossRefPubMedGoogle Scholar
  24. 24.
    Normann RA, Maynard EM, Guillory KS, Warren DJ (1996) Cortical implants for the blind. IEEE Spectrum 33:54–59CrossRefGoogle Scholar
  25. 25.
    Rizzo JF, Wyatt J (1997) Prospects for a visual prosthesis. Neuroscientist 3:251–262Google Scholar
  26. 26.
    Rizzo JF, Loewenstein J, Kelly SK, Shire DB, Herndon T, Wyatt JL (1999) Electrical stimulation of human retina with a microfabricated electrode array. Invest Ophthalmol Vis Sci 40:S783Google Scholar
  27. 27.
    Schanze T, Wilms M, Eger M, Hesse L, Eckhorn R (2002) Activation zones in cat visual cortex evoked by electrical retina stimulation. Graefes Arch Clin Exp Ophthalmol 240:947–954PubMedGoogle Scholar
  28. 28.
    Schmidt EM, Bak MJ, Hambrecht FT, Kufta CV, O’Rourke DK, Vallabhanath P (1996) Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex. Brain 119:507–522PubMedGoogle Scholar
  29. 29.
    Sharma S (1999) Ophthaproblem. Ocular ischemic syndrome. Can Fam Physician 45:901, 909PubMedGoogle Scholar
  30. 30.
    Stieglitz T, Blau C, Beutel H, Keller R, Meyer JU (1997) Konzeption und Entwicklung von flexiblen Stimulatorstrukturen innerhalb eines Retina Implant Systems [Conception and development of flexible stimulator structures within a retinal implant system]. Biomed Tech (Berl) 42[Suppl]:458–459Google Scholar
  31. 31.
    Tassiker GE (1956) US patent 2,760,783Google Scholar
  32. 32.
    Veraart C, Raftopoulos C, Mortimer JT, Delbeke J, Pins D, Michaux G, Vanlierde A, Parrini S, Wanet-Defalque MC (1998) Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode. Brain Res 813:181–186CrossRefPubMedGoogle Scholar
  33. 33.
    Wilms M (2001) Electrical receptive fields and cortical activation spread in response to electrical retina stimulation. Assessment of spatio-temporal resolution for a retina implant. PhD thesis, Department of Physics, University of Marburg, GermanyGoogle Scholar
  34. 34.
    Wyatt J, Rizzo J (1996) Ocular implants for the blind. IEEE Spectrum 33:47–53CrossRefGoogle Scholar
  35. 35.
    Zrenner E (2002) Will retinal implants restore vision? Science 295:1022–1025CrossRefPubMedGoogle Scholar
  36. 36.
    Zrenner E, Miliczek KD, Gabel VP, Graf HG, Guenther E, Haemmerle H, Hoefflinger B, Kohler K, Nisch W, Schubert M, Stett A, Weiss S (1997) The development of subretinal microphotodiodes for replacement of degenerated photoreceptors. Ophthalmic Res 29:269–280PubMedGoogle Scholar
  37. 37.
    Zrenner E, Stett A, Weiss S, Aramant RB, Guenther E, Kohler K, Miliczek KD, Seiler MJ, Haemmerle H (1999) Can subretinal microphotodiodes successfully replace degenerated photoreceptors. Vis Res 39:2555–2567CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Helmut G. Sachs
    • 1
  • Thomas Schanze
    • 2
  • Marcus Wilms
    • 2
  • Andreas Rentzos
    • 2
  • Ursula Brunner
    • 1
  • Florian Gekeler
    • 3
  • Lutz Hesse
    • 4
    • 5
  1. 1.University Eye ClinicUniversity of RegensburgRegensburgGermany
  2. 2.Applied Physics-NeuroPhysics Group, Department of PhysicsPhilipps University MarburgMarburgGermany
  3. 3.Department of Neuroophthalmology, University Eye HospitalUniversity of TuebingenTuebingenGermany
  4. 4.Department of OphthalmologyPhilipps University MarburgMarburgGermany
  5. 5.Klinikum am Gesundbrunnen-AugenklinikSLK-Kliniken Heilbronn GmbHHeilbronnGermany

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