Advertisement

A review of in vivo animal studies in retinal prosthesis research

  • Dimiter R. Bertschinger
  • Evgueny Beknazar
  • Manuel Simonutti
  • Avinoam B. Safran
  • José A. Sahel
  • Serge G. Rosolen
  • Serge Picaud
  • Joel SalzmannEmail author
Review Article

Abstract

Background

The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15 years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies.

Methods

A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed.

Results

We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18).

Conclusion

The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving field.

Keywords

Retinal implant Retinal prosthesis Artificial vision Animal Surgery Blindness 

Notes

Acknowledgement

This work is supported by Swiss National Foundation for Science (FNRS) grant No 315200–116736/1, by the Fondation en Faveur des Aveugles (Geneva, Switzerland) and by the Wilsdorf Foundation (Geneva, Switzerland).

References

  1. 1.
    Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28:92–95PubMedGoogle Scholar
  2. 2.
    Acosta AC, Espana EM, Yamamoto H, Davis S, Pinchuk L, Weber BA, Orozco M, Dubovy S, Fantes F, Parel JM (2006) A newly designed glaucoma drainage implant made of poly(styrene-b-isobutylene-b-styrene): biocompatibility and function in normal rabbit eyes. Arch Ophthalmol 124:1742–1749PubMedCrossRefGoogle Scholar
  3. 3.
    Aguirre G (1978) Retinal degenerations in the dog. I. Rod dysplasia. Exp Eye Res 26:233–253PubMedCrossRefGoogle Scholar
  4. 4.
    Aguirre G, Farber D, Lolley R, O’Brien P, Alligood J, Fletcher RT, Chader G (1982) Retinal degeneration in the dog. III. Abnormal cyclic nucleotide metabolism in rod-cone dysplasia. Exp Eye Res 35:625–642PubMedCrossRefGoogle Scholar
  5. 5.
    Aguirre GD, Rubin LF (1975) Rod-cone dysplasia (progressive retinal atrophy) in Irish setters. J Am Vet Med Assoc 166:157–164PubMedGoogle Scholar
  6. 6.
    Aguirre GD, Baldwin V, Pearce-Kelling S, Narfstrom K, Ray K, Acland GM (1998) Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis 4:23PubMedGoogle Scholar
  7. 7.
    Albini TA, Rao NA, Li A, Craft CM, Fujii GY, de Juan E Jr (2004) Limited macular translocation: a clinicopathologic case report. Ophthalmology 111:1209–1214PubMedCrossRefGoogle Scholar
  8. 8.
    Ali RR, Sarra GM, Stephens C, Alwis MD, Bainbridge JW, Munro PM, Fauser S, Reichel MB, Kinnon C, Hunt DM, Bhattacharya SS, Thrasher AJ (2000) Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat Genet 25:306–310PubMedCrossRefGoogle Scholar
  9. 9.
    Baig-Silva MS, Hathcock CD, Hetling JR (2005) A preparation for studying electrical stimulation of the retina in vivo in rat. J Neural Eng 2:S29–S38PubMedCrossRefGoogle Scholar
  10. 10.
    Binder S, Stanzel BV, Krebs I, Glittenberg C (2007) Transplantation of the RPE in AMD. Prog Retin Eye Res 26:516–554PubMedCrossRefGoogle Scholar
  11. 11.
    Bradley DC, Troyk PR, Berg JA, Bak M, Cogan S, Erickson R, Kufta C, Mascaro M, McCreery D, Schmidt EM, Towle VL, Xu H (2005) Visuotopic mapping through a multichannel stimulating implant in primate V1. J Neurophysiol 93:1659–1670PubMedCrossRefGoogle Scholar
  12. 12.
    Buyukmihci N, Aguirre G, Marshall J (1980) Retinal degenerations in the dog. II. Development of the retina in rod-cone dysplasia. Exp Eye Res 30:575–591PubMedCrossRefGoogle Scholar
  13. 13.
    Campochiaro PA, Gaskin HC, Vinores SA (1987) Retinal cryopexy stimulates traction retinal detachment formation in the presence of an ocular wound. Arch Ophthalmol 105:1567–1570PubMedCrossRefGoogle Scholar
  14. 14.
    Canola K, Angenieux B, Tekaya M, Quiambao A, Naash MI, Munier FL, Schorderet DF, Arsenijevic Y (2007) Retinal stem cells transplanted into models of late stages of retinitis pigmentosa preferentially adopt a glial or a retinal ganglion cell fate. Invest Ophthalmol Vis Sci 48:446–454PubMedCrossRefGoogle Scholar
  15. 15.
    Chan F, Bradley A, Wensel TG, Wilson JH (2004) Knock-in human rhodopsin-GFP fusions as mouse models for human disease and targets for gene therapy. Proc Natl Acad Sci U S A 101:9109–9114PubMedCrossRefGoogle Scholar
  16. 16.
    Chen SJ, Mahadevappa M, Roizenblatt R, Weiland J, Humayun M (2006) Neural responses elicited by electrical stimulation of the retina. Trans Am Ophthalmol Soc 104:252–259PubMedGoogle Scholar
  17. 17.
    Chow AY, Chow VY (1997) Subretinal electrical stimulation of the rabbit retina. Neurosci Lett 225:13–16PubMedCrossRefGoogle Scholar
  18. 18.
    Chow AY, Pardue MT, Chow VY, Peyman GA, Liang C, Perlman JI, Peachey NS (2001) Implantation of silicon chip microphotodiode arrays into the cat subretinal space. IEEE Trans Neural Syst Rehabil Eng 9:86–95PubMedCrossRefGoogle Scholar
  19. 19.
    Chow AY, Pardue MT, Perlman JI, Ball SL, Chow VY, Hetling JR, Peyman GA, Liang C, Stubbs EB Jr., Peachey NS (2002) Subretinal implantation of semiconductor-based photodiodes: durability of novel implant designs. J Rehabil Res Dev 39:313–321PubMedGoogle Scholar
  20. 20.
    Chow AY, Chow VY, Packo KH, Pollack JS, Peyman GA, Schuchard R (2004) The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch Ophthalmol 122:460–469PubMedCrossRefGoogle Scholar
  21. 21.
    Chowdhury V, Morley JW, Coroneo MT (2005) Feasibility of extraocular stimulation for a retinal prosthesis. Can J Ophthalmol 40:563–572PubMedGoogle Scholar
  22. 22.
    Chowdhury V, Morley JW, Coroneo MT (2005) Evaluation of extraocular electrodes for a retinal prosthesis using evoked potentials in cat visual cortex. J Clin Neurosci 12:574–579PubMedCrossRefGoogle Scholar
  23. 23.
    Chowdhury V, Morley JW, Coroneo MT (2005) Stimulation of the retina with a multielectrode extraocular visual prosthesis. ANZ J Surg 75:697–704PubMedCrossRefGoogle Scholar
  24. 24.
    Cleary PE, Ryan SJ (1979) Experimental posterior penetrating eye injury in the rabbit. II. Histology of wound, vitreous, and retina. Br J Ophthalmol 63:312–321PubMedCrossRefGoogle Scholar
  25. 25.
    Cleary PE, Ryan SJ (1979) Experimental posterior penetrating eye injury in the rabbit. I. Method of production and natural history. Br J Ophthalmol 63:306–311PubMedCrossRefGoogle Scholar
  26. 26.
    Colodetti L, Weiland JD, Colodetti S, Ray A, Seiler MJ, Hinton DR, Humayun MS (2007) Pathology of damaging electrical stimulation in the retina. Exp Eye Res 85:23–33PubMedCrossRefGoogle Scholar
  27. 27.
    Cordeiro MF, Constable PH, Alexander RA, Bhattacharya SS, Khaw PT (1997) Effect of varying the mitomycin-C treatment area in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci 38:1639–1646PubMedGoogle Scholar
  28. 28.
    D’Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM, Vollrath D (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9:645–651PubMedCrossRefGoogle Scholar
  29. 29.
    DeMarco PJ Jr., Yarbrough GL, Yee CW, McLean GY, Sagdullaev BT, Ball SL, McCall MA (2007) Stimulation via a subretinally placed prosthetic elicits central activity and induces a trophic effect on visual responses. Invest Ophthalmol Vis Sci 48:916–926PubMedCrossRefGoogle Scholar
  30. 30.
    Eckhorn R, Wilms M, Schanze T, Eger M, Hesse L, Eysel UT, Kisvarday ZF, Zrenner E, Gekeler F, Schwahn H, Shinoda K, Sachs H, Walter P (2006) Visual resolution with retinal implants estimated from recordings in cat visual cortex. Vision Res 46:2675–2690PubMedCrossRefGoogle Scholar
  31. 31.
    Eckmiller R (1997) Learning retina implants with epiretinal contacts. Ophthalmic Res 29:281–289PubMedCrossRefGoogle Scholar
  32. 32.
    Eger M, Wilms M, Eckhorn R, Schanze T, Hesse L (2005) Retino-cortical information transmission achievable with a retina implant. Biosystems 79:133–142PubMedCrossRefGoogle Scholar
  33. 33.
    Gekeler F, Kobuch K, Schwahn HN, Stett A, Shinoda K, Zrenner E (2004) Subretinal electrical stimulation of the rabbit retina with acutely implanted electrode arrays. Graefes Arch Clin Exp Ophthalmol 242:587–596PubMedCrossRefGoogle Scholar
  34. 34.
    Gekeler F, Szurman P, Grisanti S, Weiler U, Claus R, Greiner TO, Volker M, Kohler K, Zrenner E, Bartz-Schmidt KU (2007) Compound subretinal prostheses with extra-ocular parts designed for human trials: successful long-term implantation in pigs. Graefes Arch Clin Exp Ophthalmol 245:230–241PubMedCrossRefGoogle Scholar
  35. 35.
    Gerding H (2007) A new approach towards a minimal invasive retina implant. J Neural Eng 4:S30–37PubMedCrossRefGoogle Scholar
  36. 36.
    Gerding H, Benner FP, Taneri S (2007) Experimental implantation of epiretinal retina implants (EPI-RET) with an IOL-type receiver unit. J Neural Eng 4:S38–S49PubMedCrossRefGoogle Scholar
  37. 37.
    Ghosh F, Engelsberg K, English RV, Petters RM (2007) Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol 245:835–846PubMedCrossRefGoogle Scholar
  38. 38.
    Gouws P, Moss EB, Trope GE, Ethier CR (2007) Continuous intraocular pressure (IOP) measurement during glaucoma drainage device implantation. J Glaucoma 16:329–333PubMedCrossRefGoogle Scholar
  39. 39.
    Guven D, Weiland JD, Fujii G, Mech BV, Mahadevappa M, Greenberg R, Roizenblatt R, Qiu G, Labree L, Wang X, Hinton D, Humayun MS (2005) Long-term stimulation by active epiretinal implants in normal and RCD1 dogs. J Neural Eng 2:S65–S73PubMedCrossRefGoogle Scholar
  40. 40.
    Guven D, Weiland JD, Maghribi M, Davidson JC, Mahadevappa M, Roizenblatt R, Qiu G, Krulevitz P, Wang X, Labree L, Humayun MS (2006) Implantation of an inactive epiretinal poly(dimethyl siloxane) electrode array in dogs. Exp Eye Res 82:81–90PubMedCrossRefGoogle Scholar
  41. 41.
    Hafezi F, Grimm C, Simmen BC, Wenzel A, Reme CE (2000) Molecular ophthalmology: an update on animal models for retinal degenerations and dystrophies. Br J Ophthalmol 84:922–927PubMedCrossRefGoogle Scholar
  42. 42.
    Hämmerle H, Kobuch K, Kohler K, Nisch W, Sachs H, Stelzle M (2002) Biostability of micro-photodiode arrays for subretinal implantation. Biomaterials 23:797–804PubMedCrossRefGoogle Scholar
  43. 43.
    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 238:840–845PubMedCrossRefGoogle Scholar
  44. 44.
    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
  45. 45.
    Humayun MS (2001) Intraocular retinal prosthesis. Trans Am Ophthalmol Soc 99:271–300PubMedGoogle Scholar
  46. 46.
    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. Vision Res 43:2573–2581PubMedCrossRefGoogle Scholar
  47. 47.
    Jacobson SG, Aleman TS, Cideciyan AV, Sumaroka A, Schwartz SB, Windsor EA, Traboulsi EI, Heon E, Pittler SJ, Milam AH, Maguire AM, Palczewski K, Stone EM, Bennett J (2005) Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success. Proc Natl Acad Sci U S A 102:6177–6182PubMedCrossRefGoogle Scholar
  48. 48.
    Jin M, Chen Y, He S, Ryan SJ, Hinton DR (2004) Hepatocyte growth factor and its role in the pathogenesis of retinal detachment. Invest Ophthalmol Vis Sci 45:323–329PubMedCrossRefGoogle Scholar
  49. 49.
    Johnson L, Scribner D, Skeath P, Klein R, Ilg D, Perkins K, Helfgott M, Sanders R, Panigrahi D (2007) Impedance-based retinal contact imaging as an aid for the placement of high resolution epiretinal prostheses. J Neural Eng 4:S17–S23PubMedCrossRefGoogle Scholar
  50. 50.
    Kaluzny JJ, Jozwicki W, Wisniewska H (2007) Histological biocompatibility of new, non-absorbable glaucoma deep sclerectomy implant. J Biomed Mater Res B Appl Biomater 81:403–409PubMedGoogle Scholar
  51. 51.
    Kerdraon YA, Downie JA, Suaning GJ, Capon MR, Coroneo MT, Lovell NH (2002) Development and surgical implantation of a vision prosthesis model into the ovine eye. Clin Experiment Ophthalmol 30:36–40PubMedCrossRefGoogle Scholar
  52. 52.
    Khaw PT, Sherwood MB, Doyle JW, Smith MF, Grierson I, McGorray S, Schultz GS (1992) Intraoperative and post operative treatment with 5-fluorouracil and mitomycin-c: long term effects in vivo on subconjunctival and scleral fibroblasts. Int Ophthalmol 16:381–385PubMedCrossRefGoogle Scholar
  53. 53.
    Khaw PT, Doyle JW, Sherwood MB, Grierson I, Schultz G, McGorray S (1993) Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol 111:263–267PubMedCrossRefGoogle Scholar
  54. 54.
    Kim SY, Sadda S, Humayun MS, de Juan E Jr, Melia BM, Green WR (2002) Morphometric analysis of the macula in eyes with geographic atrophy due to age-related macular degeneration. Retina 22:464–470PubMedCrossRefGoogle Scholar
  55. 55.
    Kim SY, Sadda S, Pearlman J, Humayun MS, de Juan E Jr, Melia BM, Green WR (2002) Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Retina 22:471–477PubMedCrossRefGoogle Scholar
  56. 56.
    Komar G, Szutter L (1968) Tierärztliche Augenheilkunde. Verlag Paul Parey, BerlinGoogle Scholar
  57. 57.
    Konno T, Uchibori T, Nagai A, Kogi K, Nakahata N (2007) Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits. Life Sci 80:1115–1122PubMedCrossRefGoogle Scholar
  58. 58.
    Kuffler SW (1953) Discharge patterns and functional organization of mammalian retina. J Neurophysiol 16:37–68PubMedGoogle Scholar
  59. 59.
    Laube T, Schanze T, Brockmann C, Bolle I, Stieglitz T, Bornfeld N (2003) Chronically implanted epidural electrodes in Gottinger minipigs allow function tests of epiretinal implants. Graefes Arch Clin Exp Ophthalmol 241:1013–1019PubMedCrossRefGoogle Scholar
  60. 60.
    Lee D, Geller S, Walsh N, Valter K, Yasumura D, Matthes M, LaVail M, Stone J (2003) Photoreceptor degeneration in Pro23His and S334ter transgenic rats. Adv Exp Med Biol 533:297–302PubMedCrossRefGoogle Scholar
  61. 61.
    Li ZY, Wong F, Chang JH, Possin DE, Hao Y, Petters RM, Milam AH (1998) Rhodopsin transgenic pigs as a model for human retinitis pigmentosa. Invest Ophthalmol Vis Sci 39:808–819PubMedGoogle Scholar
  62. 62.
    Liou GI, Pakalnis VA, Matragoon S, Samuel S, Behzadian MA, Baker J, Khalil IE, Roon P, Caldwell RB, Hunt RC, Marcus DM (2002) HGF regulation of RPE proliferation in an IL-1beta/retinal hole-induced rabbit model of PVR. Mol Vis 8:494–501PubMedGoogle Scholar
  63. 63.
    Little CW, Castillo B, DiLoreto DA, Cox C, Wyatt J, del Cerro C, del Cerro M (1996) Transplantation of human fetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina. Invest Ophthalmol Vis Sci 37:204–211PubMedGoogle Scholar
  64. 64.
    Lopez R, Gouras P, Kjeldbye H, Sullivan B, Reppucci V, Brittis M, Wapner F, Goluboff E (1989) Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. Invest Ophthalmol Vis Sci 30:586–588PubMedGoogle Scholar
  65. 65.
    Luke C, Alteheld N, Aisenbrey S, Luke M, Bartz-Schmidt KU, Walter P, Kirchhof B (2003) Electro-oculographic findings after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 241:710–715PubMedCrossRefGoogle Scholar
  66. 66.
    Majji AB, Humayun MS, Weiland JD, Suzuki S, D’Anna SA, de Juan E Jr (1999) Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs. Invest Ophthalmol Vis Sci 40:2073–2081PubMedGoogle Scholar
  67. 67.
    Marc RE, Jones BW, Watt CB, Strettoi E (2003) Neural remodeling in retinal degeneration. Prog Retin Eye Res 22:607–655PubMedCrossRefGoogle Scholar
  68. 68.
    Menotti-Raymond M, David VA, Schaffer AA, Stephens R, Wells D, Kumar-Singh R, O’Brien SJ, Narfstrom K (2007) Mutation in CEP290 discovered for cat model of human retinal degeneration. J Hered 98:211–220PubMedCrossRefGoogle Scholar
  69. 69.
    Montezuma SR, Loewenstein J, Scholz C, Rizzo JF 3rd (2006) Biocompatibility of materials implanted into the subretinal space of Yucatan pigs. Invest Ophthalmol Vis Sci 47:3514–3522PubMedCrossRefGoogle Scholar
  70. 70.
    Morales M, Gomez-Cabrero A, Peral A, Gasull X, Pintor J (2007) Hypotensive effect of profilin on rabbit intraocular pressure. Eur J Pharmacol 567:145–148PubMedCrossRefGoogle Scholar
  71. 71.
    Nadig MN (1999) Development of a silicon retinal implant: cortical evoked potentials following focal stimulation of the rabbit retina with light and electricity. Clin Neurophysiol 110:1545–1553PubMedCrossRefGoogle Scholar
  72. 72.
    Nakauchi K, Fujikado T, Kanda H, Morimoto T, Choi JS, Ikuno Y, Sakaguchi H, Kamei M, Ohji M, Yagi T, Nishimura S, Sawai H, Fukuda Y, Tano Y (2005) Transretinal electrical stimulation by an intrascleral multichannel electrode array in rabbit eyes. Graefes Arch Clin Exp Ophthalmol 243:169–174PubMedCrossRefGoogle Scholar
  73. 73.
    Nakauchi K, Fujikado T, Kanda H, Kusaka S, Ozawa M, Sakaguchi H, Ikuno Y, Kamei M, Tano Y (2007) Threshold suprachoroidal-transretinal stimulation current resulting in retinal damage in rabbits. J Neural Eng 4:S50–S57PubMedCrossRefGoogle Scholar
  74. 74.
    Ogden TE, Brown KT (1964) Intraretinal responses of the cynamolgus monkey to electrical stimulation of the optic nerve and retina. J Neurophysiol 27:682–705PubMedGoogle Scholar
  75. 75.
    Olver JM, McCartney AC (1989) Anterior segment vascular casting. Eye 3(Pt 3):302–307PubMedCrossRefGoogle Scholar
  76. 76.
    Palanker D, Huie P, Vankov A, Aramant R, Seiler M, Fishman H, Marmor M, Blumenkranz M (2004) Migration of retinal cells through a perforated membrane: implications for a high-resolution prosthesis. Invest Ophthalmol Vis Sci 45:3266–3270PubMedCrossRefGoogle Scholar
  77. 77.
    Pang J, Cheng M, Stevenson D, Trousdale MD, Dorey CK, Blanks JC (2004) Adenoviral-mediated gene transfer to retinal explants during development and degeneration. Exp Eye Res 79:189–201PubMedCrossRefGoogle Scholar
  78. 78.
    Pardue MT, Ball SL, Hetling JR, Chow VY, Chow AY, Peachey NS (2001) Visual evoked potentials to infrared stimulation in normal cats and rats. Doc Ophthalmol 103:155–162PubMedCrossRefGoogle Scholar
  79. 79.
    Pardue MT, Stubbs EB Jr, Perlman JI, Narfstrom K, Chow AY, Peachey NS (2001) Immunohistochemical studies of the retina following long-term implantation with subretinal microphotodiode arrays. Exp Eye Res 73:333–343PubMedCrossRefGoogle Scholar
  80. 80.
    Pardue MT, Phillips MJ, Yin H, Fernandes A, Cheng Y, Chow AY, Ball SL (2005) Possible sources of neuroprotection following subretinal silicon chip implantation in RCS rats. J Neural Eng 2:S39–S47PubMedCrossRefGoogle Scholar
  81. 81.
    Pardue MT, Phillips MJ, Yin H, Sippy BD, Webb-Wood S, Chow AY, Ball SL (2005) Neuroprotective effect of subretinal implants in the RCS rat. Invest Ophthalmol Vis Sci 46:674–682PubMedCrossRefGoogle Scholar
  82. 82.
    Pardue MT, Ball SL, Phillips MJ, Faulkner AE, Walker TA, Chow AY, Peachey NS (2006) Status of the feline retina 5 years after subretinal implantation. J Rehabil Res Dev 43:723–732PubMedCrossRefGoogle Scholar
  83. 83.
    Pawlyk BS, Smith AJ, Buch PK, Adamian M, Hong DH, Sandberg MA, Ali RR, Li T (2005) Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP. Invest Ophthalmol Vis Sci 46:3039–3045PubMedCrossRefGoogle Scholar
  84. 84.
    Petters RM, Alexander CA, Wells KD, Collins EB, Sommer JR, Blanton MR, Rojas G, Hao Y, Flowers WL, Banin E, Cideciyan AV, Jacobson SG, Wong F (1997) Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nat Biotechnol 15:965–970PubMedCrossRefGoogle Scholar
  85. 85.
    Pinilla I, Cuenca N, Sauve Y, Wang S, Lund RD (2007) Preservation of outer retina and its synaptic connectivity following subretinal injections of human RPE cells in the Royal College of Surgeons rat. Exp Eye Res 85:381–392PubMedCrossRefGoogle Scholar
  86. 86.
    Planck SR, Andresevic J, Chen JC, Holmes DL, Rodden W, Westra I, Wu SC, Huang XN, Kay G, Wilson DJ et al (1992) Expression of growth factor mRNA in rabbit PVR model systems. Curr Eye Res 11:1031–1039PubMedCrossRefGoogle Scholar
  87. 87.
    Ray K, Baldwin VJ, Acland GM, Aguirre GD (1995) Molecular diagnostic tests for ascertainment of genotype at the rod cone dysplasia 1 (rcd1) locus in Irish setters. Curr Eye Res 14:243–247PubMedCrossRefGoogle Scholar
  88. 88.
    Rizzo JF 3rd, Wyatt J, Loewenstein J, Kelly S, Shire D (2003) Methods and perceptual thresholds for short-term electrical stimulation of human retina with microelectrode arrays. Invest Ophthalmol Vis Sci 44:5355–5361PubMedCrossRefGoogle Scholar
  89. 89.
    Rizzo JF 3rd, Wyatt J, Loewenstein J, Kelly S, Shire D (2003) Perceptual efficacy of electrical stimulation of human retina with a microelectrode array during short-term surgical trials. Invest Ophthalmol Vis Sci 44:5362–5369PubMedCrossRefGoogle Scholar
  90. 90.
    Rizzo JF 3rd, Goldbaum S, Shahin M, Denison TJ, Wyatt J (2004) In vivo electrical stimulation of rabbit retina with a microfabricated array: strategies to maximize responses for prospective assessment of stimulus efficacy and biocompatibility. Restor Neurol Neurosci 22:429–443PubMedGoogle Scholar
  91. 91.
    Sachs HG, Gekeler F, Schwahn H, Jakob W, Kohler M, Schulmeyer F, Marienhagen J, Brunner U, Framme C (2005) Implantation of stimulation electrodes in the subretinal space to demonstrate cortical responses in Yucatan minipig in the course of visual prosthesis development. Eur J Ophthalmol 15:493–499PubMedGoogle Scholar
  92. 92.
    Sachs HG, Schanze T, Brunner U, Sailer H, Wiesenack C (2005) Transscleral implantation and neurophysiological testing of subretinal polyimide film electrodes in the domestic pig in visual prosthesis development. J Neural Eng 2:S57–S64PubMedCrossRefGoogle Scholar
  93. 93.
    Sachs HG, Schanze T, Wilms M, Rentzos A, Brunner U, Gekeler F, Hesse L (2005) Subretinal implantation and testing of polyimide film electrodes in cats. Graefes Arch Clin Exp Ophthalmol 243:464–468PubMedCrossRefGoogle Scholar
  94. 94.
    Sailer H, Shinoda K, Blatsios G, Kohler K, Bondzio L, Zrenner E, Gekeler F (2007) Investigation of thermal effects of infrared lasers on the rabbit retina: a study in the course of development of an active subretinal prosthesis. Graefes Arch Clin Exp Ophthalmol 245:1169–1178PubMedCrossRefGoogle Scholar
  95. 95.
    Sakaguchi H, Fujikado T, Fang X, Kanda H, Osanai M, Nakauchi K, Ikuno Y, Kamei M, Yagi T, Nishimura S, Ohji M, Yagi T, Tano Y (2004) Transretinal electrical stimulation with a suprachoroidal multichannel electrode in rabbit eyes. Jpn J Ophthalmol 48:256–261PubMedCrossRefGoogle Scholar
  96. 96.
    Salzmann J, Linderholm OP, Guyomard JL, Paques M, Simonutti M, Lecchi M, Sommerhalder J, Dubus E, Pelizzone M, Bertrand D, Sahel J, Renaud P, Safran AB, Picaud S (2006) Subretinal electrode implantation in the P23H rat for chronic stimulations. Br J Ophthalmol 90:1183–1187PubMedCrossRefGoogle Scholar
  97. 97.
    Santos A, Humayun MS, de Juan E Jr, Greenburg RJ, Marsh MJ, Klock IB, Milam AH (1997) Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis. Arch Ophthalmol 115:511–515PubMedCrossRefGoogle Scholar
  98. 98.
    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 240:947–954PubMedCrossRefGoogle Scholar
  99. 99.
    Schanze T, Greve N, Hesse L (2003) Towards the cortical representation of form and motion stimuli generated by a retina implant. Graefes Arch Clin Exp Ophthalmol 241:685–693PubMedCrossRefGoogle Scholar
  100. 100.
    Schanze T, Sachs HG, Wiesenack C, Brunner U, Sailer H (2006) Implantation and testing of subretinal film electrodes in domestic pigs. Exp Eye Res 82:332–340PubMedCrossRefGoogle Scholar
  101. 101.
    Schanze T, Hesse L, Lau C, Greve N, Haberer W, Kammer S, Doerge T, Rentzos A, Stieglitz T (2007) An optically powered single-channel stimulation implant as test system for chronic biocompatibility and biostability of miniaturized retinal vision prostheses. IEEE Trans Biomed Eng 54:983–992PubMedCrossRefGoogle Scholar
  102. 102.
    Schwahn HN, Gekeler F, Kohler K, Kobuch K, Sachs HG, Schulmeyer F, Jakob W, Gabel VP, Zrenner E (2001) Studies on the feasibility of a subretinal visual prosthesis: data from Yucatan micropig and rabbit. Graefes Arch Clin Exp Ophthalmol 239:961–967PubMedCrossRefGoogle Scholar
  103. 103.
    Shah HA, Montezuma SR, Rizzo JF 3rd (2006) In vivo electrical stimulation of rabbit retina: effect of stimulus duration and electrical field orientation. Exp Eye Res 83:247–254PubMedCrossRefGoogle Scholar
  104. 104.
    Sheedlo HJ, Li L, Turner JE (1993) Effects of RPE age and culture conditions on support of photoreceptor cell survival in transplanted RCS dystrophic rats. Exp Eye Res 57:753–761PubMedCrossRefGoogle Scholar
  105. 105.
    Siu T, Morley J (2008) Implantation of episcleral electrodes via anterior orbitotomy for stimulation of the retina with induced photoreceptor degeneration: an in vivo feasibility study on a conceptual visual prosthesis. Acta Neurochir (Wien) 150:477–485CrossRefGoogle Scholar
  106. 106.
    Siu TL, Morley JW (2008) In vivo evaluation of an episcleral multielectrode array for stimulation of the retina with reduced retinal ganglion cell mass. J Clin Neurosci 15:552–558PubMedCrossRefGoogle Scholar
  107. 107.
    Stasi K, Paccione J, Bianchi G, Friedman A, Danias J (2006) Photodynamic treatment in a rabbit model of glaucoma surgery. Acta Ophthalmol Scand 84:661–666PubMedCrossRefGoogle Scholar
  108. 108.
    Stone JL, Barlow WE, Humayun MS, de Juan E Jr, Milam AH (1992) Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch Ophthalmol 110:1634–1639PubMedCrossRefGoogle Scholar
  109. 109.
    Sugie Y, Yoshikawa M, Ouji Y, Saito K, Moriya K, Ishizaka S, Matsuura T, Maruoka S, Nawa Y, Hara Y (2005) Photoreceptor cells from mouse ES cells by co-culture with chick embryonic retina. Biochem Biophys Res Commun 332:241–247PubMedCrossRefGoogle Scholar
  110. 110.
    Takahashi M, Miyoshi H, Verma IM, Gage FH (1999) Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J Virol 73:7812–7816PubMedGoogle Scholar
  111. 111.
    Tschernutter M, Schlichtenbrede FC, Howe S, Balaggan KS, Munro PM, Bainbridge JW, Thrasher AJ, Smith AJ, Ali RR (2005) Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther 12:694–701PubMedCrossRefGoogle Scholar
  112. 112.
    Vergara O, Ogden T, Ryan S (1989) Posterior penetrating injury in the rabbit eye: effect of blood and ferrous ions. Exp Eye Res 49:1115–1126PubMedCrossRefGoogle Scholar
  113. 113.
    Veske A, Nilsson SE, Narfstrom K, Gal A (1999) Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65. Genomics 57:57–61PubMedCrossRefGoogle Scholar
  114. 114.
    Volker M, Shinoda K, Sachs H, Gmeiner H, Schwarz T, Kohler K, Inhoffen W, Bartz-Schmidt KU, Zrenner E, Gekeler F (2004) In vivo assessment of subretinally implanted microphotodiode arrays in cats by optical coherence tomography and fluorescein angiography. Graefes Arch Clin Exp Ophthalmol 242:792–799PubMedCrossRefGoogle Scholar
  115. 115.
    Vollrath D, Feng W, Duncan JL, Yasumura D, D’Cruz PM, Chappelow A, Matthes MT, Kay MA, LaVail MM (2001) Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci U S A 98:12584–12589PubMedCrossRefGoogle Scholar
  116. 116.
    Walter P, Szurman P, Vobig M, Berk H, Ludtke-Handjery HC, Richter H, Mittermayer C, Heimann K, Sellhaus B (1999) Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits. Retina 19:546–552PubMedCrossRefGoogle Scholar
  117. 117.
    Walter P, Kisvarday ZF, Gortz M, Alteheld N, Rossler G, Stieglitz T, Eysel UT (2005) Cortical activation via an implanted wireless retinal prosthesis. Invest Ophthalmol Vis Sci 46:1780–1785PubMedCrossRefGoogle Scholar
  118. 118.
    Weber M, Rabinowitz J, Provost N, Conrath H, Folliot S, Briot D, Cherel Y, Chenuaud P, Samulski J, Moullier P, Rolling F (2003) Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery. Mol Ther 7:774–781PubMedCrossRefGoogle Scholar
  119. 119.
    Weiland JD, Yanai D, Mahadevappa M, Williamson R, Mech BV, Fujii GY, Little J, Greenberg RJ, de Juan E Jr, Humayun MS (2004) Visual task performance in blind humans with retinal prosthetic implants. Conf Proc IEEE Eng Med Biol Soc 6:4172–4173PubMedGoogle Scholar
  120. 120.
    Wilms M, Eckhorn R (2005) Spatiotemporal receptive field properties of epiretinally recorded spikes and local electroretinograms in cats. BMC Neurosci 6:50PubMedCrossRefGoogle Scholar
  121. 121.
    Yamauchi Y, Franco LM, Jackson DJ, Naber JF, Ziv RO, Rizzo JF, Kaplan HJ, Enzmann V (2005) Comparison of electrically evoked cortical potential thresholds generated with subretinal or suprachoroidal placement of a microelectrode array in the rabbit. J Neural Eng 2:S48–S56PubMedCrossRefGoogle Scholar
  122. 122.
    Yanai D, Weiland JD, Mahadevappa M, Greenberg RJ, Fine I, Humayun MS (2007) Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am J Ophthalmol 143:820–827PubMedCrossRefGoogle Scholar
  123. 123.
    Zeng Y, Takada Y, Kjellstrom S, Hiriyanna K, Tanikawa A, Wawrousek E, Smaoui N, Caruso R, Bush RA, Sieving PA (2004) RS-1 Gene Delivery to an Adult Rs1h Knockout Mouse Model Restores ERG b-Wave with Reversal of the Electronegative Waveform of X-Linked Retinoschisis. Invest Ophthalmol Vis Sci 45:3279–3285PubMedCrossRefGoogle Scholar
  124. 124.
    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 29:269–280PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Dimiter R. Bertschinger
    • 1
  • Evgueny Beknazar
    • 1
  • Manuel Simonutti
    • 2
  • Avinoam B. Safran
    • 1
  • José A. Sahel
    • 2
    • 3
  • Serge G. Rosolen
    • 2
    • 3
  • Serge Picaud
    • 2
    • 3
  • Joel Salzmann
    • 1
    Email author
  1. 1.Geneva University Eye ServiceGeneva 14Switzerland
  2. 2.INSERM UMR-S592, Laboratoire de Physiopathologie Cellulaire et Moléculaire de la RétineInstitut de la VisionParisFrance
  3. 3.Fondation Ophtalmologique A.de RothschildParisFrance

Personalised recommendations