OU-MRU Vol.8 Mar 2015

Okayama University Medical Research Updates （OU-MRU）

2015.03 Vol.8

Source: Okayama University, Center for Public Affairs and Communications
For immediate release: 11 March 2015
Okayama University research: Light-responsive dye stimulates sight in genetically blindpatients(Okayama, 11 March) Researchers at Okayama demonstrate the promise of a new
approach for stimulating neurons in the eyes of patients with dead photoreceptor cells.
“The basic concept of retinal prostheses is to replace dead photoreceptor cells with artificialdevices,” explain in a review of their recent research Toshihiko Matsuo, eye doctor, andTetsuya Uchida, polymer scientist, from Okayama University, in collaboration with Kenichi
Takarabe, semiconductor scientist, from Okayama University of Science in Japan. Blindpatients with hereditary diseases such as retinitis pigmentosa, have dead photoreceptor
cells but other neurons remain alive. The Okayama University researchers are exploiting theworking functions of these living neurons to send messages to the brain by artificial
stimulation from photoelectric dyes that respond to light.

Other work on retinal prostheses has focused on the use of arrays of electrodes – as in adigital camera – or photodiodes. The challenges with these approaches include miniaturising
the devices, biocompatibility, low sensitivity and low currents which often demand an
external power source. “The prototype of the photoelectric dye-coupled retinal prosthesis,
OURePTM, is unique in using electric potentials to stimulate retinal neurons, in contrast withthe other systems of retinal prostheses that generate electric currents,” ” say the Okayama
University researchers.
Kelvin probe studies confirmed the presence of electric potentials on the film surface
induced in rapid response to light. The researchers also tested the effect of the dye in theeyes of Royal College of Surgeons rats. Cytotoxicity analyses proved promising andbehavioural tests on the rats suggested that the treatment was effective.

In addition the researchers have plans for ways of testing the likelihood of treatment
success by using optical coherence tomography to assess the level of degeneration in thepatient’s retina. In terms of coming work they say, “Clinical studies of photoelectric dyeOKAYAMA University
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 Japan© OKAYAMA University

OU-MRU Vol.8 Mar 2015

based retinal prostheses, OURePTM, in patients with retinitis pigmentosa who lose sight will
be planned since the manufacturing control and the quality control have been alreadyestablished for the medical device.”

Background
The photoelectric dye
The Okayama researchers used the dye 2-[2-[4-[dibutylamino)phenyl]ethenyl]-3carboxymethylbenzothiazolium bromide ,which has an absorption spectra that spans thevisible range from 400 nm to 600 nm. It is also stable, readily synthesised and has a low
molecular weight and no obvious toxic components.
They coupled the photoelectric dye to a soft thin polyethylene film at a concentration ofaround 106 dye molecules per μm2. The film could also be rolled up before inserting into thesubretinal area through a small opening so that a large film could be fitted providing a large
field of view.

SafetyPolyethylene has been used for medical implants for some time and its safety and stability
has already been proved. The researchers tested the toxicity of the dye in vitro using
cultured retinal cells, as these are the cells the dye would come into contact with first. No
cytotoxicity was observed. Furthermore, no toxicity has been found for OURePTM or for thephotoelectric dye in any tests for biological evaluation of medical devices, based on theInternational Organization for Standardization (ISO) 10993.
The photoelectric dye coupled polyethylene film was then implanted into the retina of living
rats. Apoptosis was reduced in the retinal neurons which were in contact with dye-coupled
polyethylene film, OURePTM. The photoelectric dye may have a neuroprotective effect on
retinal neurons. Further tests are needed.

Efficacy
Kelvin probe measurements of the electric potential on the dye-coupled film surface when
exposed to light showed rapid responses over the same range of wavelengths as the known
absorption spectrum of the dye. The sensitivity to different light intensities was alsopromising.

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OU-MRU Vol.8 Mar 2015

The researchers tested the dye on chick embryo retinal cells in vitro using a fluorescent dyeto monitor calcium ions. They found that the dye-stimulated responses triggered theincreased calcium ion concentrations. Dye coupled films were also implanted into Royal
College of Surgeons rats, who were then subjected to behaviour tests. When the rats wereplaced in a drum with spinning walls painted in white and black vertical stripes, the rats
moved in the direction of the rotating stripes, suggesting some level of sight had been
retrieved.

Reference
Matsuo T, Uchida T, Takarabe K. Safety, efficacy, and quality control of a photoelectric dyebased retinal prosthesis (Okayama University-type retinal prosthesis) as a medical device. JArtif Organs 2009;12:213-225.
DOI 10.1007/s10047-009-0471-6
Alamusi, Matsuo T, Hosoya O, Tsutsui KM, Uchida T. Behavior tests andimmunohistochemical retinal response analyses in RCS rats with subretinal implantation of
Okayama-University-type retinal prosthesis. J Artif Organs. 2013 Sep;16(3):343-51.
DOI 10.1007/s10047-013-0697-1
Alamusi, Matsuo T, Hosoya O, Tsutsui KM, Uchida T. Vision maintenance and retinalapoptosis reduction in RCS rats with Okayama University-type retinal prosthesis (OURePTM)
implantation. J Artif Organs. 2015.
DOI 10.1007/s10047-015-0825-1
Photoelectric dye-coupled thin film as a novel type of retinal prosthesis. Okayama Univ. eBulletin Vol.8, September 2014.
http://www.okayama-u.ac.jp/user/kouhou/ebulletin/ipe/vol8/ipe_001.html

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OU-MRU Vol.8 Mar 2015

Figure caption
Behaviour test to establish the presence of sight in Royal College of Surgeons rats withretinal prosthesis implantation. The researchers rotated a drum with black-and-whitevertical stripes either clockwise or anticlockwise at a slow speed of 2 or 4 rpm. A rat that
had prosthetic retinal implants was put in a round transparent-walled cage inside the drum.
Instances when the rat turned its head in a direction consistent with the direction of drum
rotation were counted as indications that the rat had retrieved some level of sight.

Correspondence toAssociate Professor Toshihiko Matsuo, M.D., Ph.D.
Department of Ophthalmology, Okayama University
Medical School and Graduate School of Medicine,
Dentistry, and Pharmaceutical Sciences, 2-5-1Shikata-cho, Kita-ku, Okayama 700-8558, Japan
E-mail: matsuot@cc.okayama-u.ac.jp
Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
Planning and Public Information Division, Okayama University
E-mail: www-adm@adm.okayama-u.ac.jp
Website: http://www.okayama-u.ac.jp/index_e.html
Okayama Univ. e-Bulletin：http://www.okayama-u.ac.jp/user/kouhou/ebulletin/

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OU-MRU Vol.8 Mar 2015

Okayama University Medical Research Updates （OU-MRU）
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Vol.5：Cell injections get to the heart of congenital defects
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Vol.7：Anticancer virus solution provides an alternative to surgery
About Okayama University
Okayama University is one of the largest
comprehensive universities in Japan withroots going back to the Medical Training
Place sponsored by the Lord of Okayama
and established in 1870. Now with 1,300
faculty and 14,000 students, the University
offers courses in specialties ranging frommedicine and pharmacy to humanities
and physical sciences. Okayama
University is located in the heart of Japan
approximately 3 hours west of Tokyo byShinkansen.

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