advances in retinal implant technology-p9 may 2012 rhine-waal university of applied sciences,...
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3 May 2012 Rhine-Waal University of Applied Sciences, Emmerich
Advances in retinal implant technology
Andrew Kuznetsov
Freiburg i.Br.
Strategies
• electronic implants (top-down)
– subretinal implants
– epiretinal implant
• cell implants
– stem cells
• gene implants (bottom-up)
– optogenetic therapy (creation of light-sensitive retinal ganglion cells)
photoreceptor cells:95% rods, 5% cones
loss of photoreceptor cells in the visual perception channel
leads to loss of vision
Clinical problems
• over 25m people around the world are visually impaired and that will rise to 50m by 2020
• retinitis pigmentosa (RP) and age-related macular degeneration(AMD) cause a degeneration of the retina
normRP dry AMD
History of artificial vision
• 1755, Charles LeRoy, visual sensations of light by passing a chargethrough the eye of a blind man
• 1929, Ottfricd Foerster, electrical stimulation of the cerebral cortexresulted in phosphenes
• 1956, Graham Tassiker, subretinal light-sensitive selenium cell transiently restored the blind patient’s ability to perceive phosphenes
• 1997, Rolf Eckmiller, first epiretinal implant• ...
22 projects on artificial vision in 2007
the discovery of
phosphenes in 1755
Gerding, 2008
The eye and retinal implants
~100 fold compression:from 131m photoreceptor cellsto 1.2m ganglion neurons
human eye
c - Argus II, d – Alpha IMS, f - Boston Retinal Implant
epiretinal implants:
fixing is difficultdon’t need intact opticseditorial processing
subretinal implants:
easy fixingneed intact opticsnative stimulation
Gerding, 2008
Boston Retinal Implant Project • Joseph Rizzo, John Wyatt• subretinal implant
• 3x5 electrodes
• 3 pigs, > 7 months
Shire et al, 2009
Second Sight, Argus II
• Alan Litke
• epiretinal implant
• on the market in spring 2011• 2-year clinical trial• 23 of 30 patients read large fonts• 6x10 electrodes (in future 200,
512 electrodes, diameter 5 µm)
http://2-sight.eu/
(a) scleral band, coil receiving power and data, electronics to process data, ribbon cable passing through the sclera to the
implant (b) video camera, transmission coil, control unit reducing the image resolution to 6x10 pixels
Retina Implant AG, Alpha IMS• Eberhart Zrenner
• subretinal implant
• microchip and external power supply through a cable
• micro photodiode array (MPA), 30x50 light sensors
• implants were removed after 4 months
http://www.eye.uni-tuebingen.de/retina-implant/videos/2
Stingl et al, 2012
Bionic Eye with IR projection
array with pillars of 10 µm in diameter and 65 µm in height
pillar electrodes (1) penetrating into retina,return electrodes (2) are located on photodiodes
rat retina after implantation of the array intoa subretinal space. Tops of pillars achieveproximity to cells in the inner nuclear layer
alternative:cells are attracted by the holes in a newly designed array
Loudin et al, 2007
Daniel Palanker
Obstacles and development
• Despite some successes, these electronic implants remain open-loop devices with poorly understood mechanisms of action
– new image preprocessing methods
– new systems design
• How many electrodes are required?– 20/80 vision, d < 7 µm, 2.5m electrodes/cm2
• Problems– delivery of information about thousands of pixels
– signal processing that compensates the loss of retinal network
– placement of electrodes close to target cells
– interaction between electrodes
– energy dissipation and electrolysis
• Early development projects– new biocompatible materials (parylene C),
– nano-structured implants, novel electrodes to exceed 100m/cm2
– ambient light operations in a contact lens
Cell and gene implants– no FDA-approved therapy for the
retinitis pigmentosa (RP)
• Stem cells ophthalmology– engineering scaffold to support
cell transplants
• Ocular gene therapy– the immune-privileged status of
the eye
– gene transfer mediated by adeno-associated viruses (AAV)
– transfection of bipolar or ganglion cells
– induced photosensitivity with channelrhodopsin-2 (Chop2)
– RetroSense Therapeutics, http://www.retro-sense.com/
retina analysis in light and dark
conditionsIvanova et al, 2010
Reading and acknowledgements
• Shire et al., Development and implantation of a minimally invasive, wireless sub-retinal neurostimulator // IEEE Trans. Biomed. Eng. 2009; 56/10: 2502-11
• Humayun et al., Interim Results from the International Trial // Ophthalmology 2012; 119: 779-88
• Sahni et al., Therapeutic Challenges to Retinitis Pigmentosa: From Neuroprotectionto Gene Therapy // Current Genomics 2011; 12: 276-84
• Ivanova et al., Retinal channelrhodopsin-2-mediated activity in vivo evaluated with manganese-enhanced magnetic resonance imaging // Molecular Vision 2010; 16: 1059-1067
• Many thanks for supporting materials to
– Prof. Gislin Dagnelie, Johns Hopkins Univ. Sch. of Medicine, Baltimore
– Prof. Kareem Zaghloul, Institute of Neurological Disorders and Stroke, Bethesda
• Thanks to Prof. Thorsten Brandt suggesting the topic
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