Photoelectric dye-based retinal prosthesis (OUReP) as a novel type of artificial retina

Toshihiko Matsuo, Tetsuya Uchida

Abstract


We have developed the world's first novel type of artificial retina, OUReP (Okayama University Retinal Prosthesis), in which a photoelectric dye that converts light energy into electric potential is covalently bonded to the surface of a polyethylene thin film as an insulator. The receptor that absorbs light and the output device that generates displacement current to stimulate nearby neurons are integrated in a sheet of thin film. It has become possible to measure the surface potential of the artificial retina OUReP using a Kelvin probe that measures the surface potential of semiconductors. When light is turned on and off to the artificial retina OUReP, the surface potential changes rapidly. As the light intensity is increased, the potential change on the surface of the artificial retina becomes larger. As for safety, the artificial retina OUReP was not toxic in all tests for biological evaluation of medical devices. As for efficacy, the artificial retina OUReP was implanted under the retina by vitreous surgery in monkey eyes which had chemically-induced macular degeneration with photoreceptor cell loss. Over the next 6 months, retinal detachment did not occur during the course, and the artificial retina was in contact with the retinal tissue. The amplitude of the visual evoked potential attenuated by macular degeneration recovered 1 month after implantation of the artificial retina, and the recovery of amplitude was maintained until 6 months after the implantation. By using multielectrode array-mounted dish recording system, it has been proved that action potential spikes are induced when the artificial retina is placed on degenerative retinal tissue of retinal dystrophic rats or mice and exposed to light, which is used as an index of the effectiveness of the artificial retina. We have established manufacturing and quality control of the device in a clean room facility, proved the safety and efficacy, and are preparing for first-in-human investigator-initiated clinical trials.


Keywords


artificial retina; retinal prosthesis; photoelectric dye; polyethylene film; monkey surgery; multielectrode array dish recording; vitrectomy; disposable injector; sustainable development goals

Full Text:

PDF

References


Humayun MS, de Juan E Jr, Dagnelie G. The bionic eye: a quarter century of retinal prosthesis research and development. Ophthalmology 2016;123(10S):S89-S97.

Matsuo T. A simple method for screening photoelectric dyes towards their use for retinal prostheses. Acta Med Okayama 2003;57:257-260.

Okayama University (Assignee). Matsuo T, Dan-oh Y, Suga S (Inventors). Agent for inducing receptor potential. United States Patent. Patent No.: US 7,101,533 B2. Date of Patent: September 5, 2006.

Okayama University (Assignee), Uchida T, Matsuo T (Inventors). Method for producing artificial retina. United States Patent. Patent No. : US10,039,861 B2. Date of Patent : August 7, 2018.

Uchida T, Ishimaru S, Shimamura K, Uji A, Matsuo T, Ohtsuki H. Immobilization of photoelectric dye on the polyethylene film surface. Memoirs of the Faculty of Engineering Okayama University 2005;39:16-20.

Uji A, Matsuo T, Ishimaru S, Kajiura A, Shimamura K, Ohtsuki H, Dan-oh Y, Suga S. Photoelectric dye-coupled polyethylene film as a prototype of retinal prostheses. Artif Organs 2005;29:53-57.

Uji A, Matsuo T, Uchida T, Shimamura K, Ohtsuki H. Intracellular calcium response and adhesiveness of chick embryonic retinal neurons to photoelectric dye-coupled polyethylene films as prototypes of retinal prostheses. Artif Organs 2006;30:695-703.

Alamusi, Matsuo T, Hosoya O, Tsutsui MK, Uchida T. Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama University-type retinal prosthesis. J Artif Organs 2013;16:343-351.

Alamusi, Matsuo T, Hosoya O, Tsutsui MK, Uchida T. Vision maintenance and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prosthesis (OURePTM) implantation. J Artif Organs 2015;18:264-271.

Alamusi, Matsuo T, Hosoya O, Uchida T. Visual evoked potential in RCS rats with Okayama University-type retinal prosthesis (OURePTM) implantation. J Artif Organs 2017;20:158-165.

Matsuo T, Uchida T, Yamashita K, Takei S, Ido D, Fujiwara A, Iino M, Oguchi M. Vision evaluation by functional observational battery, operant behavior test, and light/dark box test in retinal dystrophic RCS rats versus normal rats. Heliyon 2019;5:e01936.

Tamaki T, Matsuo T, Hosoya O, Tsutsui KM, Uchida T, Okamoto K, Uji A, Ohtsuki H. Glial reaction to photoelectric dye-based retinal prostheses implanted in the subretinal space of rats. J Artif Organs 2008;11:38-44.

Matsuo T, Uchida T, Takarabe K. Safety, efficacy, and quality control of a photoelectric dye-based retinal prosthesis (Okayama University-type retinal prosthesis) as a medical device. J Artif Organs 2009;12:213-225.

Matsuo T, Sakurai M, Terada K, Uchida T, Yamashita K, Tanaka T, Takarabe K. Photoelectric dye-coupled polyethylene film: photoresponsive properties evaluated by Kelvin probe and in vitro biological response detected in dystrophic retinal tissue of rats. Adv Biomed Eng 2019;8:137-144.

Guinand A, Noble S, Frei A, Renard J, Tramer MR, Burri H. Extra-cardiac stimulators: what do cardiologists need to know? Europace 2016;18:1299-1307.

Miocinovic S, Somayajula S, Chitnis S, Vitek JL. History, applications, and mechanisms of deep brain stimulation. JAMA Neurol 2013;70:163-171.

Edwards CA, Kouzani A, Lee KH, Ross EK. Neurostimulation devices for the treatment of neurologic disorders. Mayo Clin Proc 2017;92:1427-1444.

Muralt P. Micromachined infrared detectors based on pyroelectric thin films. Rep Prog Phys 2001;64:1339-1388.

Wang ZL. On Maxwell’s displacement current for energy and sensors: the origin of nanogenerators. Mater Today 2017;20:74-82.

Loeb GE, Peck RA, Moore WH, Hood K. BIONTM system for distributed neural prosthetic interfaces. Med Eng Phys 2001;23:9-18.

Huang F, Bladon J, Lagoy RC, Shorrock PN Jr, Hronik-Tupaj M, Zoto CA, Connors RE, Grant McGimpsey W, Molnar P, Lambert S, Rittenhouse AR, Lambert CR. A photosensitive surface capable of inducing electrophysiological changes in NG108-15 neurons. Acta Biomater 2015;12:42-50.

Okamoto K, Matsuo T, Tamaki T, Uji A, Ohtsuki H. Short-term biological safety of a photoelectric dye used as a component of retinal prostheses. J Artif Organs 2008;11:45-51.

Liu S, Matsuo T, Hosoya O, Uchida T. Photoelectric dye used for Okayama University-type retinal prosthesis reduces the apoptosis of photoreceptor cells. J Ocul Pharmacol Ther 2017;33:149-160.

Matsuo T, Uchida T, Nitta M, Yamashita K, Takei S, Ido D, Tanaka M, Oguchi M, Furukawa T. Subretinal implantation of Okayama University-type retinal prosthesis (OURePTM) in canine eyes by vitrectomy. J Vet Med Sci 2017;79:1939-1946.

Matsuo T, Uchida T, Yamashita K, Takei S, Ido D, Tanaka M, Oguchi M, Furukawa T. Visual evoked potential in rabbits’ eyes with subretinal implantation by vitrectomy of Okayama University-type retinal prosthesis (OURePTM). J Vet Med Sci 2018;80:247-259.

Matsuo T, Uchida T, Sakurai J, Yamashita K, Matsuo C, Araki T, Yamashita Y, Kamikawa K. Visual evoked potential recovery by subretinal implantation of photoelectric dye-coupled thin film retinal prosthesis (OURePTM) in monkey eyes with macular degeneration. Artif Organs 2018;42:E186-E203.

Matsuo T, Uchida T, Yamashita K, Matsuo C, Kawakami Y, Hitomi T, Taga K, Sanada T, Yamashita Y, Kuramoto K. Novel disposable injector (OUReP Injector) tested in rabbits’ eyes for subretinal implantation of Okayama University-type retinal prosthesis (OUReP). Anim Eye Res 2018;37:1-12.

Matsuo T, Matsuo C, Uchida T, Yamashita K, Tanaka T, Kawakami Y, Hitomi T, Taga K, Sanada T, Yamashita Y. Curved-tip disposable injector (OUReP Injector) to insert photoelectric dye-coupled polyethylene film (OUReP) as retinal prosthesis into subretinal space of rabbit eyes. J Surg Tech Proc 2020;4:1040.

Matsuo T, Terada K, Sakurai M, Liu S, Yamashita K, Uchida T. Step-by-step procedure to test photoelectric dye-coupled polyethylene film as retinal prosthesis to induce light-evoked spikes in isolated retinal dystrophic tissue of rd1 mice. Clin Surg 2020;5:2903.

Matsuo T, Morimoto N. Visual acuity and perimacular retinal layers detected by optical coherence tomography in patients with retinitis pigmentosa. Br J Ophthalmol 2007;91:888-890.

Tamaki M, Matsuo T. Optical coherence tomographic parameters as objective signs for visual acuity in patients with retinitis pigmentosa, future candidates for retinal prostheses. J Artif Organs 2011;14:140-150. Erratum 2011;14:385.




DOI: http://dx.doi.org/10.18103/imr.v7i1.916

Refbacks

  • There are currently no refbacks.
Copyright 2016. All rights reserved.