WO2018199493A1 - Dispositif de rétine artificielle épirétinienne et système imitant un mécanisme physiologique de cellules rétiniennes - Google Patents

Dispositif de rétine artificielle épirétinienne et système imitant un mécanisme physiologique de cellules rétiniennes Download PDF

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Publication number
WO2018199493A1
WO2018199493A1 PCT/KR2018/003900 KR2018003900W WO2018199493A1 WO 2018199493 A1 WO2018199493 A1 WO 2018199493A1 KR 2018003900 W KR2018003900 W KR 2018003900W WO 2018199493 A1 WO2018199493 A1 WO 2018199493A1
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WIPO (PCT)
Prior art keywords
substrate
retina
artificial
cell layer
retinal
Prior art date
Application number
PCT/KR2018/003900
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English (en)
Korean (ko)
Inventor
김정석
김성우
남동흔
Original Assignee
가천대학교 산학협력단
고려대학교 산학협력단
(의료)길의료재단
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Application filed by 가천대학교 산학협력단, 고려대학교 산학협력단, (의료)길의료재단 filed Critical 가천대학교 산학협력단
Publication of WO2018199493A1 publication Critical patent/WO2018199493A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36057—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for stimulating afferent nerves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0543—Retinal electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36046—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of the eye
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36103—Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems

Definitions

  • retinitis pigmentosa is a progressive retinal degenerative disease caused by dysfunction of the photoreceptor in the retina.
  • the retinitis photoreceptor and the retinal pigment epithelium are the main lesions in both eyes. Is characteristic.
  • the prevalence of RP is reported to be one in 5,000 people worldwide.
  • One of the three retinal diseases, age-related macular degeneration (AMD) is one of the three major blindness disorders, and the prevalence is increasing due to the rapid aging of the population.
  • AMD age-related macular degeneration
  • AMD AMD patients often experience worse vision in a relatively short period of time, and it is reported that the degree of real life impairment and psychological atrophy due to eyes is greater in AMD patients than other diseases.
  • sub-type retinas allow for a natural feel in the recognition of objects by using existing visual transmission pathways through bipolar cells and information processing in the inner layer of the retina.
  • the microelectrode array is inserted into the eye to allow natural eye movement, compared to the fact that in a system with a small camera mounted on glasses, the head must be turned, not the eye, in the direction of the object to see and recognize the object. This can be said to have advantages in physiological and natural aspects.
  • the number of pixels produced by the subretinal stimulation method is the largest among the artificial retinas made so far, the possibility of achieving high resolution has been suggested.
  • the Alpha IMS model which has been commercialized by Retina Implant, Germany, has 1500 photodiode arrays and matching biphasic current generation arrays, but clinical trials show that the actual resolution is 63 channel epi. It is reported to be less than the resolution of the type retina.
  • the present invention provides an epitaxial artificial retinal device and a system in which an epithelial cell has a stimulation mechanism similar to that of a sub-type retinal with a bipolar cell as a primary electrical stimulation object, and a stimulation method that simulates a natural physiological mechanism can be achieved. To provide.
  • the artificial retinal apparatus is located on the back of the substrate, and further demodulator for restoring the data of the external camera received by the optical receiver and distributing the restored information to the plurality of needle electrodes arrayed It may include.
  • the artificial retina device further comprises a cable for electrically connecting the optical receiver located on the front of the substrate and the demodulator located on the back of the substrate, wherein the cable does not penetrate the substrate.
  • the optical receiver and the demodulator may be connected along a surface of the substrate.
  • the artificial retina device comprises: a power coil wound around the outer periphery of the substrate to generate AC power; And a rectifier positioned in front of the substrate and converting AC power generated by the power coil into direct current.
  • the needle electrode has a length of 160 ⁇ m to 240 ⁇ m can be inserted up to the bipolar cell layer before the cell layer.
  • the present invention provides an epi-retinal system, comprising: a camera module for capturing visual information in front of a user and outputting an optical signal corresponding to the visual information; And a photoreceptor provided in an epiretinal layer of the retina, a photoreceiver positioned in front of the substrate and receiving light emitted from the camera module and passing through the lens, and located at a rear surface of the substrate and in a cell layer of the retina.
  • the present invention is a structure in which the optical receiver is disposed on the front surface of the substrate, compared with the structure of the conventional epi artificial retina in which the optical receiver and the electrode are disposed on the rear surface of the substrate.
  • a needle electrode structure having a length of about 200 ⁇ m is formed on the rear surface of the substrate such that the synapse of the bipolar cell is the primary electrical stimulation target.
  • This needle electrode structure invades the cell layer of the fragile retina so that it stably fixes the substrate without bioglue or tack, and makes the operation extremely easy, and the end of the needle can apply electrical stimulation directly to the synaptic layer of the bipolar cell. do.
  • the present invention has a stimulation pathway similar to the subtype artificial retina that is inserted into the cell layer to directly stimulate bipolar cells as action potentials.
  • the present invention is an epitaxial retinal device that can simulate a natural physiological mechanism even though it is an epitaxial retinal device, and does not require high voltage power generation to directly stimulate the bipolar cell, so that the epitaxial retinal device must be implemented as a conventional expensive CMOS semiconductor. Compared to the above, there is an advantage in that it is possible to guarantee the reliability of the stimulator while significantly reducing the manufacturing cost.
  • FIG 1 shows an anatomy of the retina for explaining the position where the epi-type retinal device and the sub-type retinal device are described.
  • FIG 2 illustrates an artificial retinal system according to an embodiment of the present invention.
  • FIG 3 shows an artificial retina device according to an embodiment of the present invention.
  • FIG 2 shows an artificial retinal system according to an embodiment of the present invention
  • Figure 3 shows an artificial retinal device 10 according to an embodiment of the present invention.
  • the retinal system may include a camera module 30 worn by a user and an artificial retinal device 10 implanted in the retina.
  • the eyeball has a structure including the retina (5), nerve tissue (7), choroid, sclera, cornea (1), pupil (3), iris and ciliary body.
  • the epi-type retinal device is located in front of the retina 5, and the sub-type retinal device is located behind the retina 5.
  • the retina 5 has a multilayer structure of ganglion cells, amacrine cells, bipolar cells, horizontal cells, rod cones, and pigment epithelium.
  • the retina 5 is largely divided into a retinal neuronal cell layer 51, a bipolar cell layer 53, and a rod cone 55 layer.
  • the optical receiver 103 may be positioned in front of the substrate 101 and receive light transmitted from the external camera 30 and transmitted through the lens 3.
  • the optical receiver 103 may include a plurality of photodiodes in the form of an array and may receive a digital signal processed compressed signal from an external camera 30.
  • the optical receiver 103 may receive external visual information as infrared light.
  • the optical receiver 103 may receive visible light, but has a disadvantage in that it is not good for a user or a third party due to the light continuously lit when the transmission and reception with the external camera 30 is made of visible light. Therefore, it is preferable that the external camera 30 also transmits an optical signal to the infrared region, and the optical receiver 103 is also provided as an IR optical receiver including an infrared sensor to produce a natural aesthetics.
  • the electrode structure according to the present embodiment is particularly effective in reducing the ease of surgery and the manufacturing cost in epitaxial retina.
  • the conventional epi artificial retina stimulates the retinal nerve cell layer 51, so that a high current is required.
  • the conventional epitaxial retina is applied with a high voltage at the output terminal of the stimulator, and a high voltage transistor must be used to withstand the high compliance voltage. This is not only expensive, but also has a high mismatch, which has a disadvantage of degrading performance.
  • the needle electrode 107 according to the present embodiment is thin and long to reach the bipolar cell layer 53 through the retinal nerve cell layer 51 so that a high current is required for the needle electrode 107 to directly stimulate the bipolar cell. And there is no high compliance voltage at the output of the stimulator array. Therefore, a general process transistor may be used for the artificial retina device 10 according to the present embodiment.
  • Needle electrode 107 is preferably inserted to the point where the synapse of the bipolar cell layer 53 before the cell layer 55 is located.
  • the retinal nerve cell layer 51 to the end of the bipolar cell layer 53 has a length of about 200 ⁇ m 250 ⁇ m. Therefore, the needle electrode 107 according to the present embodiment is formed to have a length of 160 ⁇ m to 240 ⁇ m so that the needle electrode 107 does not invade the rod cone 55 cell layer and has a length sufficient to stimulate the synapse of the bipolar cell layer 53. It is desirable to have.
  • FIG. 3A illustrates a front perspective view of the artificial retina device 10 according to the present embodiment
  • FIG. 3B illustrates a rear perspective view of the artificial retina device 10 according to the present embodiment
  • the elongated shape of the needle electrode 107 is omitted in order to understand the rear layout of the substrate 101.
  • a plurality of needle electrodes 107 are configured on the rear surface of the substrate 101 and receive signals from the optical receiver 103 through the demodulator 111 and through the voltage regulator 113. Receives power for driving.
  • the demodulator 111 is located at the rear of the substrate 101, restores data of the external camera 30 received by the optical receiver 103, and distributes the restored information to the plurality of needle electrodes 107 arrayed. Can be.
  • the demodulator 111 may include a circuit capable of generating a current based on the restored signal.
  • the demodulator 111 may generate a bi-phasic current having two phases of a cathode and an anode for balancing charges to be transmitted to the nerve.
  • the biphasic current to be discharged at the end of the needle electrode 107 can be balanced so that negative and positive charges are canceled out so that charges of either polarity do not accumulate in the optic nerve 7.
  • the conversion circuit of the demodulator 111 for outputting the active potential in the form of biphasic current may be used in a conventional circuit structure.
  • the rectifier 105 may be positioned in front of the substrate 101, and may convert AC power generated by the power coil 110 into direct current.
  • the rectifier 105 may include a direct current conversion element such as a schottky diode and a capacitor, and is preferably implemented using a discrete element in consideration of a difficulty in on-chiping a semiconductor process.
  • the rectifier 105 is positioned in front of the substrate 101 that is not inserted into the cell layer of the retina to perform stable signal processing. Power output from the rectifier 105 may be delivered through the cable 108 to the back of the substrate 101.
  • the power coil 110 may be wound around the outer circumference of the substrate 101 to generate AC power.
  • the wound position may be wound on the substrate 101 inside the eyeball, but may be performed to be wound outward of the eyeball in consideration of the convenience of surgery.
  • the power coil 110 may be an RF coil.
  • the power coil 110 may receive external wireless power flowing from the outside. The larger the diameter of the power coil 110 can receive a large amount of flux (flux), the efficiency is improved and is particularly suitable as a power supply means of the artificial retina device (10).
  • the voltage regulator 113 is located at the rear of the substrate 101, and may distribute the power output from the rectifier 105 to each end of the array of the plurality of needle electrodes 107.
  • the distribution voltage of the voltage regulator 113 may be significantly lower than the conventional compliance voltage, because the reason is that it is due to the structure of the needle electrode 107 that directly stimulates the anode cell layer 53. same.
  • the cable 108 may electrically connect the rectifier 105 positioned at the front of the substrate 101 and the voltage regulator 113 positioned at the rear of the substrate 101.
  • the cable 108 may in this case also connect the rectifier 105 and the voltage regulator 113 along the surface of the substrate 101 without penetrating the substrate 101.
  • the cable 108 connecting the optical receiver 103 and the demodulator 111 is called a first cable 108 (a), and a cable connecting the rectifier 105 and the voltage regulator 113 ( 108 is referred to as a second cable 108 (b).
  • both the first and second cables 108 are connected to the demodulator 111 and the voltage regulator 113 on the rear side by half-winding the substrate 101. .
  • This may be understood in consideration of the manufacturing cost of the substrate 101 is difficult to perforate. That is, in the artificial retina device 10 according to the present embodiment, the essential components are separated into the front and rear surfaces of the substrate 101 in consideration of the characteristics of the deeply inserted electrode structure. It is preferable that the lower surface cable 108 does not penetrate the substrate 101 and connects the front and rear configurations by circumferentially surrounding the side surfaces of the substrate 101.
  • the retinal device 10 according to the present embodiment is a side of the package guard 109
  • the bracket configuration performs the above function.
  • the camera module 30 may capture visual information in front of the user and output an optical signal corresponding to the visual information.
  • the camera module 30 may include a camera 301 for capturing an image, a signal processor 303, and an optical transmitter 305.
  • the camera 301 captures an external image signal and may be a CCD camera or a CMOS camera.
  • the camera 301 may be modularized and built on a device that is easy for a user to wear, such as glasses.
  • the signal processor 303 may digitally process the visual information captured by the camera 301 to reinforce the edge of the object, and transmit the signal processed visual information to the optical transmitter 305.
  • the signal processor 303 may convert image information captured by the camera 301 into image information.
  • the signal processor 303 may perform an additional signal processing process of the converted image information and, as an example, may emphasize the edge of an object in the image.
  • the optical transmitter 305 may transmit light at an intensity corresponding to the pixel of the image information transmitted from the signal processor 303.
  • the light output from the optical transmitter 305 may pass through the lens 3 of the user and enter the optical receiver 103 of the artificial retina device 10.

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Abstract

La présente invention concerne un dispositif de rétine artificielle épirétinienne pour stimuler le nerf optique en réponse à des informations visuelles d'un objet capturé par une caméra externe, le dispositif comprenant : un substrat disposé sur la couche épirétinienne de la rétine; un récepteur optique disposé sur la surface avant du substrat de façon à recevoir la lumière émise par la caméra externe et transmise à travers la lentille oculaire; et une pluralité d'électrodes aiguilles disposées sur la surface arrière du substrat, insérées dans la couche cellulaire de la rétine de façon à fixer le substrat, et à stimuler les cellules bipolaires en réponse à un signal optique reçu par le récepteur optique, chacune des électrodes aiguilles ayant une forme conique avec une pointe aiguë et une longueur prédéterminée, et la pointe aiguë pouvant atteindre jusqu'à la couche de cellule bipolaire de la rétine de façon à stimuler directement les cellules bipolaires.
PCT/KR2018/003900 2017-04-28 2018-04-03 Dispositif de rétine artificielle épirétinienne et système imitant un mécanisme physiologique de cellules rétiniennes WO2018199493A1 (fr)

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KR1020170055441A KR101979994B1 (ko) 2017-04-28 2017-04-28 망막 세포의 생리적 기전을 모사한 에피형 인공망막 장치 및 시스템
KR10-2017-0055441 2017-04-28

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112206414A (zh) * 2020-08-25 2021-01-12 浙江大学 一种视网膜假体及其加工方法

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KR102196461B1 (ko) * 2019-08-27 2020-12-29 아주대학교산학협력단 에피형 인공망막 장치
KR102408304B1 (ko) * 2020-01-23 2022-06-14 재단법인대구경북과학기술원 변형 가능한 망막 전극 장치
KR102373657B1 (ko) 2020-02-04 2022-03-15 한국과학기술연구원 인공망막용 미세전극 배열체의 제조 방법
KR102168044B1 (ko) * 2020-07-22 2020-10-20 주식회사 셀리코 고해상도 인공망막 장치를 위한 고속 무선 데이터 수신 장치
KR102332169B1 (ko) * 2021-02-24 2021-12-01 주식회사 셀리코 증강현실 기반의 인공망막 시스템

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JP2004057628A (ja) * 2002-07-31 2004-02-26 Nidek Co Ltd 視覚再生補助装置
JP2005279000A (ja) * 2004-03-30 2005-10-13 Nidek Co Ltd 視覚再生補助装置
JP2010187747A (ja) * 2009-02-16 2010-09-02 Nidek Co Ltd 視覚再生補助装置
KR101275215B1 (ko) * 2011-04-29 2013-06-17 서울대학교산학협력단 고해상도 인공 망막 자극기
US8706243B2 (en) * 2009-02-09 2014-04-22 Rainbow Medical Ltd. Retinal prosthesis techniques

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004057628A (ja) * 2002-07-31 2004-02-26 Nidek Co Ltd 視覚再生補助装置
JP2005279000A (ja) * 2004-03-30 2005-10-13 Nidek Co Ltd 視覚再生補助装置
US8706243B2 (en) * 2009-02-09 2014-04-22 Rainbow Medical Ltd. Retinal prosthesis techniques
JP2010187747A (ja) * 2009-02-16 2010-09-02 Nidek Co Ltd 視覚再生補助装置
KR101275215B1 (ko) * 2011-04-29 2013-06-17 서울대학교산학협력단 고해상도 인공 망막 자극기

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112206414A (zh) * 2020-08-25 2021-01-12 浙江大学 一种视网膜假体及其加工方法

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