大阪府保険医協会 Acta Medica Okayama 54 713 2026 『光が見える』人工網膜の可能性 ― 有機色素分子を部材とする世界初の医療機器「光電変換色素薄膜型人工網膜OUReP」 13 21 EN Toshihiko Matsuo Tetsuya Uchida Hiroshi Ishikane 　網膜色素変性や加齢黄斑変性では、光を細胞膜電位に変換する網膜視細胞が死んでいるが、視神経として脳に連絡する神経節細胞は生き残っている。人工網膜は視細胞を代替する人工物で、光を受け電流を出力する電極アレイ型が主流であるが、電流は拡散するため解像度向上が難しい。そこで人工網膜の解像度向上を目指して、光を電位差に変換する光電変換色素分子を絶縁体のポリエチレン薄膜表面に共有結合した光電変換色素薄膜型の人工網膜OURePを開発してきた。この人工網膜OURePは光受容と電位出力の一体型で外部起電力は不要、手術では薄膜を鋏で切って眼内に植込む大きさを自由に選べる。使い捨てインジェクタを使って薄膜を丸め眼球の網膜下に硝子体手術で植込み、網膜下に植込んだ人工網膜OURePは光を受けて電位差を出力し隣接する網膜組織の神経細胞の活動電位を誘発する。クリーンルームで製造品質管理を行い、安全性と有効性を証明して、医師主導治験を準備している。今後、日本の国民皆保険が維持できるよう比較安価な適正価格の人工網膜治療を提供したい。 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0969-0239 32 16 2025 Development of sulfation for cellulose pulp to change its fiber morphology and appearance to transparent in water 9663 9677 EN Ayato Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tetsuya Uchida Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Cellulose pulp (CP) is composed mainly of cellulose which is one of the most useful and sustainable natural polymers. Cellulose-based materials, such as completely dispersed nanofibers and water-soluble cellulose, are transparent in water. Additionally, chemical modification of CP has been employed as a pretreatment for the preparation of nanofibers and to impart absorption properties derived from anionic functional groups. However, little is known about chemically modified CPs comprising micron-scale fibers that are transparent in water.In this study, we synthesized transparent sulfated cellulose pulp (TSCP) that exhibits good dispersion stability, high transparency in water, and highly swollen fiber structures. The sulfation method involved heating sulfamic acid and urea supported on CP. TSCP synthesized using a sulfamic acid amount relative to CP (Q) of 18.5, a molar ratio of urea to sulfamic acid (R) of 0.80, and a reaction temperature of 140 °C exhibited the highest total light transmittance (94.7%) in water, a degree of polymerization (535), and amount of sulfate groups (1.73 mmol/g). Polarization microscopy confirmed that most TSCP fibers swelled in water along the fiber width direction. The structure of hydrous-state TSCP was further confirmed using low-vacuum scanning electron microscopy. The maximum fiber width of the swollen TSCP reached 122 μm, which was approximately six times than that of CP. The crystallinity was equivalent to that of the original CP with a Cellulose I-type crystalline structure. This transparent, hydrous-state TSCP, comprising predominantly swollen CP fibers, demonstrates potential for applications as a transparent material. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 140 2025 Advances in filler-crosslinked membranes for hydrogen fuel cells in sustainable energy generation 745 776 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Mamun Shahriar Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Siow Hwa Teo Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah M. Azizur R. Khan Department of Chemistry, Jashore University of Science and Technology Yun Hin Taufiq-Yap Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia Suman C. Mohanta Department of Chemistry, Jashore University of Science and Technology Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mrs Eti Awual Institute for Chemical Research, Kyoto University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University Hussein Znad Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Fuel cell membranes can be used in various ways to achieve zero-emission transport and energy systems, which offer a promising way to power production due to their higher efficiency compared to the internal combustion engine and the eco-environment. Perfluoro sulfonic acid membranes used for proton exchange membranes (PEMs) have certain drawbacks, like higher fuel permeability and expense, lower mechanical and chemical durability, and proton conductivity under low humidity and above 80 °C temperature. Researchers have drawn their attention to the production of polymer electrolyte membranes with higher proton conductivity, thermal and chemical resilience, maximum power density, lower fuel permeability, and lower expense. For sustainable clean energy generation, a review covering the most useful features of advanced material-associated membranes would be of great benefit to all interested communities. This paper endeavors to explore several types of novel inorganic fillers and crosslinking agents, which have been incorporated into membrane matrices to design the desired properties for an advanced fuel cell system. Membrane parameters such as proton conductivity, the ability of H2 transport, and the stability of the membrane are described. Research directions for developing fuel cell membranes are addressed based on several challenges suggested. The technological advancement of nanostructured materials for fuel cell applications is believed to significantly promote the future clean energy generation technology in practice. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0360-3199 101 2025 Next frontier in photocatalytic hydrogen production through CdS heterojunctions 173 211 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Abdul Malek Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Farzana Yeasmin Nipa Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Obayed Raihan Department of Pharmaceutical Sciences, College of Health Sciences and Pharmacy, Chicago State University Hasan Mahmud Bangladesh Energy and Power Research Council (BEPRC) Md. Elias Uddin Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Mohd Lokman Ibrahim School of Chemistry and Environment, Faculty of Applied Sciences, Universiti Teknologi MARA G. Abdulkareem-Alsultan Catalysis Science and Technology Research Centre, Faculty of Science, Universiti Putra Malaysia Alam Hossain Mondal USAID - Bangladesh Advancing Development and Growth through Energy (BADGE) Project, Tetra Tech Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Mrs Eti Awual Institute for Chemical Research, Kyoto University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Photocatalytic hydrogen (H₂) generation via solar-powered water splitting represents a sustainable solution to the global energy crisis. Cadmium sulfide (CdS) has emerged as a promising semiconductor photocatalyst due to its tunable bandgap, high physicochemical stability, cost-effectiveness, and widespread availability. This review systematically examines recent advancements in CdS-based heterojunctions, categorized into CdS-metal (Schottky), CdS-semiconductor (p-n, Z-scheme, S-scheme), and CdS-carbon heterojunctions. Various strategies employed to enhance photocatalytic efficiency and stability are discussed, including band structure engineering, surface modification, and the incorporation of crosslinked architectures. A critical evaluation of the underlying photocatalytic mechanisms highlights recent efforts to improve charge separation and photostability under operational conditions. This review highlights the challenges and opportunities in advancing CdS-based photocatalysts and provides a direction for future research. The insights presented aim to accelerate the development of efficient and durable CdS-based photocatalysts for sustainable H₂ production. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0001-8686 343 2025 Progress in silicon-based materials for emerging solar-powered green hydrogen (H2) production 103558 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Siow Hwa Teo Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah Hasan Mahmud Bangladesh Energy and Power Research Council (BEPRC) A.M. Swaraz Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mrs Eti Awual Department of Chemistry, Graduate School of Science, Osaka University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University Hussein Znad Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University The imperative demand for sustainable and renewable energy solutions has precipitated profound scientific investigations into photocatalysts designed for the processes of water splitting and hydrogen fuel generation. The abundance, low toxicity, high conductivity, and cost-effectiveness of silicon-based compounds make them attractive candidates for hydrogen production, driving ongoing research and technological advancements. Developing an effective synthesis method that is simple, economically feasible, and environmentally friendly is crucial for the widespread implementation of silicon-based heterojunctions for sustainable hydrogen production. Balancing the performance benefits with the economic and environmental considerations is a key challenge in the development of these systems. The specific performance of each catalyst type can vary depending on the synthesis method, surface modifications, catalyst loading, and reaction conditions. The confluence of high crystallinity, reduced oxygen concentration, and calcination temperature within the silicon nanoparticle has significantly contributed to its noteworthy hydrogen evolution rate. This review provides an up-to-date evaluation of Si-based photocatalysts, summarizing recent developments, guiding future research directions, and identifying areas that require further investigation. By combining theoretical insights and experimental findings, this review offers a comprehensive understanding of Si-based photocatalysts for water splitting. Through a comprehensive analysis, it aims to elucidate existing knowledge gaps and inspire future research directions towards optimized photocatalytic performance and scalability, ultimately contributing to the realization of sustainable hydrogen generation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0032-3896 2023 Preparation of crystalline polyimide nanofibers via solution crystallization EN Shota Kumano Graduate School of Natural Science and Technology, Okayama University Tomoyasu Takaki Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Graduate School of Natural Science and Technology, Okayama University Two crystalline polyimide nanofibers (PINFs) with different morphologies were prepared. The crystalline unit cells of the aromatic PI crystals and the crystal morphologies of the fabricated PINFs were examined. PINF-I (lengths = 305 ± 152 nm and diameters = 12 ± 2 nm) was crystallized from crystalline PI dissolved in a concentrated sulfuric acid solution. The resulting PINF-I was isolated from this solution, and it did not aggregate in water. PINF-II with diameters of 105 ± 99 nm was prepared by dispersing PINF-I in a mixed water and t-butanol (TBA) solution (water:TBA = 4:1), followed by freeze-drying. Then, the PINF-II was heated to enhance its crystallinity. X-ray diffraction and transmission electron microscopy studies of the heat-treated PINF-II revealed a PI crystalline unit cell [orthorhombic, a = 1.21 nm, b = 0.88 nm, and c = 2.23 nm (molecular chain axis direction)]. The crystal structure of the heat-treated PINF-II suggested that highly crystalline PINFs were fabricated in which the PI molecular chains were oriented along the direction of the fiber lengths. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1042-7147 33 8 2022 Preparation of cellulose nanocrystals coated with polymer crystals and their application in composite films 2511 2518 EN Tetsuya Uchida Graduate School of Natural Science and Technology, Okayama University Ryohei Nishioka Graduate School of Natural Science and Technology, Okayama University Risa Yanai Graduate School of Natural Science and Technology, Okayama University Increasing the dispersibility of cellulose nanocrystals (CNCs) as a reinforcing material is highly desirable to obtain composites with enhanced mechanical properties. To this aim, nanocomposite fibers (NCF(CNC/polymer)) were fabricated by coating CNCs with polymer crystals. Poly(vinyl alcohol) (PVA) and poly(vinyl alcohol-co-ethylene) (EVOH) were crystallized from a dilute solution in the presence of CNCs, which acted as nucleating agents for polymer crystal growth on the CNC surface. NCF consisting of CNCs coated with PVA crystals (NCF(CNC/PVA)) and CNCs coated with EVOH crystals (NCF(CNC/EVOH)) were successfully obtained. Both NCF(CNC/polymer) showed good dispersibility in water, even after drying, and were used to prepare composite films with improved mechanical properties. The reinforcement effect of NCF(CNC/PVA) was greater than that of pure CNCs and NCF(CNC/EVOH). The PVA composite films exhibited optical transmittance above 99% compared with additive-free PVA films. No agglomerates appeared even under the optical microscopic observation of the PVA composite film, and NCF(CNC/PVA) dispersibility was extremely good. NCF(CNC/PVA)-added PVA composite films exhibited increased glass transition temperature compared with additive-free PVA films, and the crystallinity of the PVA film increased. The highly dispersed CNCs in the PVA matrix and the increase in the glass transition temperature and crystallinity caused an increase in the mechanical modulus of the PVA composite film at low NCF(CNC/PVA) content. Furthermore, the effect of the morphologies of cellulose nanofibers and CNCs on the mechanical properties of the composite films prepared using the respective NCFs was investigated. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1042-7147 2021 Preparation of highly porous heat‐resistant polybenzoxazole network films and their electrical conductivities 1 EN Tetsuya Uchida Graduate School of Natural Science and Technology Okayama University Yukihisa Onishi Graduate School of Natural Science and Technology Okayama University Atsu Goto Graduate School of Natural Science and Technology Okayama University Highly porous rigid polybenzoxazole (PBO) network films were prepared using a precursor-mediated fabrication method. The obtained PBO network films possessed high porosities of similar to 40%, as calculated from their apparent densities. In addition, the 5%-weight-loss temperatures of the films were >= 570 degrees C under nitrogen atmosphere, demonstrating an excellent thermal stability. The electrical conductivities of the obtained PBO network films and phosphoric-acid-doped PBO network films were also evaluated. In addition, PBO network films containing pyridine rings were prepared and subjected to phosphoric acid doping. The resultant films were found to exhibit the highest conductivities of the films considered in this study owing to proton conduction both between phosphate groups and between the pyridine rings. The highest conductivity was found for a film prepared from a phosphoric-acid-doped PBO network containing pyridine rings, that is, 2.09 x 10(-1) S/cm at 150 degrees C, which was higher than that of Nafion (TM). Therefore, these films can be used at higher temperatures than that of Nafion (TM). No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0167577X 307 2021 Clarification of degradation mechanism on retinal prosthesis using photoelectric dyes coupled to polyethylene film by mass spectrometry 130978 EN Koichiro Yamashita Graduate School of Natural Science and Technology, Okayama University Mayu Mitsui Graduate School of Natural Science and Technology, Okayama University Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tetsuya Uchida Graduate School of Natural Science and Technology, Okayama University Photoelectric dyes have stimulated retinal neurons by absorbing light and generating an electric potential. Therefore, a photoelectric dye was used to develop a retinal prosthesis to restore vision loss due to retinitis pigmentosa. The retinal prosthesis, referred to as a dye-coupled film, was prepared by chemically coupling the dyes to a polyethylene film surface through amide bonds. However, the coupled dyes decreased during an implantation test in a monkey eye. This study clarifies the degradation mechanism of the dye-coupled film. Since the dyes were selectively coupled to the film surface, it is difficult to detect the eliminated dyes in a solution. Therefore, a model compound that mimicked the chemical structure of the dye-coupled film by converting the carboxylic acid of dye to the amide bond is used. It was found that the elimination of the side chain, including the amide bond, occurred before the degradation of the conjugated structure according to mass spectrometry of the model compound. The degradation mechanism of the dye-coupled film was predicted based on that of the model compound. It was concluded that chemical bonds between the dye and the film surface were preferentially decomposed, leading to the detachment of the dyes from the film surface. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-1729 11 6 2021 Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence 591 EN Toshihiko Matsuo Department of Ophthalmology, Okayama University Hospital Shihui Liu Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Tetsuya Uchida Polymer Materials Science, Okayama University Graduate School of Natural Science and Technology Satomi Onoue Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka Shinsaku Nakagawa Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University Mayumi Ishii Drug Discovery Initiative, The University of Tokyo Kayoko Kanamitsu Drug Discovery Initiative, The University of Tokyo NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1741-2560 18 4 2021 Modelling the visual response to an OUReP retinal prosthesis with photoelectric dye coupled to polyethylene film 045006 EN Koichiro Yamashita Graduate School of Natural Science and Technology, Okayama University Prathima Sundaram Department of Electrical and Computer Engineering, University of Toronto Tetsuya Uchida Graduate School of Natural Science and Technology, Okayama University Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Willy Wong Department of Electrical and Computer Engineering, University of Toronto Objective. Retinal prostheses have been developed to restore vision in blind patients suffering from diseases like retinitis pigmentosa. Approach. A new type of retinal prosthesis called the Okayama University-type retinal prosthesis (OUReP) was developed by chemically coupling photoelectric dyes to a polyethylene film surface. The prosthesis works by passively generating an electric potential when stimulated by light. However, the neurophysiological mechanism of how OUReP stimulates the degenerated retina is unknown. Main results. Here, we explore how the OUReP affects retinal tissues using a finite element model to solve for the potential inside the tissue and an active Hodgkin-Huxley model based on rat vision to predict the corresponding retinal bipolar response. Significance. We show that the OUReP is likely capable of eliciting responses in retinal bipolar cells necessary to generate vision under most ambient conditions. No potential conflict of interest relevant to this article was reported.

IOP Publishing Acta Medica Okayama 1748-6041 16 4 2021 Development of highly durable retinal prosthesis using photoelectric dyes coupled to polyethylene film and quantitative in vitro evaluation of its durability 045001 EN Koichiro Yamashita Graduate School of Natural Science and Technology, Okayama University Tenu Tanaka Graduate School of Natural Science and Technology, Okayama University Toshihiko Matsuo Graduate School of Interdisciplinary Science and Engineering in Health Systems Tetsuya Uchida Graduate School of Natural Science and Technology, Okayama University Retinal prostheses have been developed to restore vision in blind patients suffering from such diseases as retinitis pigmentosa. In our previous studies, we developed a retinal prosthesis called dye-coupled film by chemical coupling of photoelectric dyes, which absorb light and then generate electrical potential, with a polyethylene film surface. The dye-coupled film is nontoxic, and we recovered the vision of a monkey with macular degeneration. The amount of dye on the dye-coupled film, however, decreased to one-third after five months in the monkey’s eye. The photoelectric dye consists of a cation with photoresponsivity and a bromide ion (Br−). Therefore, an anion-exchange reaction could be applied to the dye-coupled film to improve its durability. In this study, the anion-exchange reaction was conducted using bis(trifluoromethanesulfonyl)imide ion (TFSI−), which has lower nucleophilicity than Br−. First, the long-term durability was examined without using animal subjects and in a short period. Subsequently, an elemental analysis was performed to confirm the exchange between Br− and TFSI−, and chemical properties, such as photoresponsivity and durability, before and after the anion exchange, were evaluated. It was quantitatively confirmed that the long-term durability of dye-coupled films can be evaluated in an in vitro environment and in a short period of one-thirtieth by utilizing a saline solution at 60°C, compared with an in vivo environment. In addition, the durability of the dye-coupled film with TFSI− was improved to 270%–320% compared with that of the dye-coupled film with Br−. No potential conflict of interest relevant to this article was reported.

National Library of Medicine Acta Medica Okayama 2470-3524 7 1 2021 Photoelectric dye-based retinal prosthesis (OUReP) as a novel type of artificial retina EN Toshihiko Matsuo Ophthalmology, Okayama University Hospital Tetsuya Uchida olymer Materials Science, Okayama University Graduate School of Natural Science and Technology, 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. No potential conflict of interest relevant to this article was reported.

Remedy Acta Medica Okayama 4 3 2020 Curved-Tip Disposable Injector (OUReP Injector) to Insert Photoelectric Dye-Coupled Polyethylene Film (OUReP) as Retinal Prosthesis into Subretinal Space of Rabbit Eyes 1040 EN Toshihiko Matsuo Department of Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Chie matsuo Department of Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems Tetsuya Uchida Department of Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology Koichiro Yamashita Department of Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology Tenu Tanaka Department of Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology Yusuke Kawakami Minori Industry Co. Ltd. Toshiya Hitomi Minori Industry Co. Ltd. Kanji Taga Minori Industry Co. Ltd. Tatsuya Sanada Minori Industry Co. Ltd. Yusuke Yamashita Shin Nippon Biomedical Laboratories Ltd. The photoelectric dye-coupled thin polyethylene film functions as a novel type of retinal prosthesis in subretinal space of the eye. We previously reported a novel disposable injector to insert the thin film into subretinal space of the rabbit eye by vitreous surgery. The injection system composed of two separate parts, injector and loader. A circular film in 5 mm to 10 mm diameter was pulled into a transparent tube of the loader with a commercial 25-gauge forceps. The loader tube was joined with a sleeve to tube tip of the injector. The film in the loader was pushed with a plunger for the loader into the injector tube tip. The loader with the sleeve was removed from the injector tip, and the tube tip with the film was filled with solution. This study reported a small-bore curved-tip disposable injector with outer diameter of 1.6 mm. A curved-tip polypropylene tube was formed by the process of heating and cooling of the tube inserted with a curved guide wire. The plunger for the curved-tip tube was made of a polyphenylsulfone tip connected with a press-fitting inner polypropylene tube to a nylon rod. Bleb retinal detachment in 4 surgically aphakic eyes of rabbits were induced by infusing solution into subretinal space with a 38-gauge polyimide tip, and a retinal tear was made at the edge of retinal detachment with 25-gauge diathermy. The injector tip with the rolled film in 6 mm diameter was inserted from 2 mm wide scleral incision into vitreous and then into subretinal space. The rolled films were released into subretinal space with the tip end inserted into the retinal tear, and the released films were confirmed to stay under the retina with no additional aid. Dissection one month after surgeries confirmed successful implantation of 4 films into subretinal space of each rabbit eye. The curved-tip injector could release the rolled film into the subretinal space without additional effort, compared with the straight-tip injector, and would help surgeons implant photoelectric dye-coupled thin film retinal prosthesis easily at vitreous surgery. No potential conflict of interest relevant to this article was reported.

Remedy Acta Medica Okayama 2474-1647 5 2020 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 2903 EN Toshihiko Matsuo Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems Keiko Terada Research Center, Techno Pro, Inc. Mikako Sakurai Research Center, Techno Pro, Inc. Shihu Liu Regenerative and Reconstructive Medicine (Ophthalmology), Okayama University Medical School and Graduate School of Interdisciplinary Science and Engineering in Health Systems Koichiro Yamashita Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology Tetsuya Uchida Polymer Materials Science, Okayama University Faculty of Engineering and Graduate School of Natural Science and Technology Purpose: Multielectrode array recording for electric activity in cardiac and neuronal cells has been developed as preclinical tests for drug screening. This study aims to establish an in vitro assay system, using the multielectrode array, to record light-evoked spikes in isolated degenerative retinal tissues of retinal dystrophic rd1 mouse, as a preclinical test to examine the efficacy of photoelectric dye-coupled thin film retinal prosthesis.</br> Methods: Light-evoked spike response was tested for 1 min at first step in the isolated degenerative retinal tissue of retinal dystrophic rd1 mouse only on the multielectrode array, tested in the same retinal tissue overlain with a plain control film for light-off and light-on 10 min each at second step, and tested in the same tissue overlain with a dye-coupled film at third step. The retinal tissues which showed light-evoked response at first or second step were not used for evaluation at third step.</br> Results: Residual light-evoked spikes were recorded at first or second step in 18 of 35 retinal tissues (51%) at 6 weeks of the age in rd1 mice, 16 of 44 tissues (36%) at 7 weeks, and 10 of 39 tissues (25%) at 8 weeks. At third step, light-evoked spikes were recorded with dye-coupled films in 8 of 17 retinal tissues (47%) at 6 weeks, 10 of 28 tissues (35%) at 7 weeks, and 8 of 29 tissues (27%) at 8 weeks.</br> Conclusion: A step-by-step procedure with internal control was established to measure light-evoked spikes by the multielectrode array in the isolated degenerative retinal tissue to evaluate photoelectric dye-coupled thin films. This preclinical study would present one line of evidence for the efficacy of photoelectric dye-coupled thin film retinal prosthesis towards a first-in-human clinical trial. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0032-3861 202 2020 Preparation of solution-grown lozenge-shaped poly(p-phenylene terephthalamide) single crystals and their structural stabilization by heat treatment 122672 EN Tetsuya Uchida Graduate School of Natural Science and Technology, Okayama University Yutaro Hara Graduate School of Natural Science and Technology, Okayama University Tomoyasu Takaki Graduate School of Natural Science and Technology, Okayama University In this study, the preparation of poly (p-phenylene terephthalamide) (PPTA) single crystals was examined using crystallization from dilute solutions in concentrated sulfuric acid. Lozenge-shaped PPTA single crystals were successfully prepared using a self-seeding method with a low degree of supercooling, and they consisted of modification I crystals. The a-axis direction of the crystal corresponded to the long diagonal direction of the rhombus, the b-axis direction with the short diagonal direction, and the PPTA molecular chain direction (the c-axis direction) with the crystal's thickness direction. In addition, the PPTA single crystals had a (110) growth plane, where the thickness of each single crystal was approximately equal to the molecular chain length of the PPTA. Upon heat treatment of the PPTA single crystals, the symmetry changed from P1a1 to the more stable P11n. In addition, the heat treatment caused a difference in the density of each symmetric crystal, resulting in crack formation along the b-axis direction, which is the hydrogen-bonding direction. However, the heat treatment did not change the thickness of the PPTA single crystals. Conversely, the isothermal crystallization of the PPTA caused progression in the crystallization only under a high degree of supercooling, thus yielding plate-like PPTA crystals that consisted of modification II crystals. In these plate-like PPTA crystals, the length corresponded to the crystal a-axis direction, and the electron diffraction pattern was broad. Furthermore, the equilibrium dissolution temperature of the PPTA single crystals was discussed. No potential conflict of interest relevant to this article was reported.

Elsevier Science Acta Medica Okayama 24058440 5 6 2019 Vision evaluation by functional observational battery, operant behavior test, and light/dark box test in retinal dystrophic RCS rats versus normal rats e01936 EN Toshihiko Matsuo Ophthalmology, Okayama University Medical School and Okayama University Hospital Tetsuya Uchida Polymer Materials Science, Okayama University Graduate School of Natural Science and Technology Koichiro Yamashita Polymer Materials Science, Okayama University Graduate School of Natural Science and Technology Shigiko Takei Ina Research Daisuke Ido Ina Research Atsushi Fujiwara Ina Research Masahiko Iino Ina Research Masao Oguchi Ina Research BACKGROUND:<br/> Vision plays a key role in some behavior tests for rats. Okayama University-type retinal prosthesis (OUReP) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. This study aims to assess vision in retinal dystrophic (RCS) rats, in comparison with normal rats, by selected behavior tests. We also examined whether the tests could detect vision changes in RCS rats with dye-coupled film implantation.<br/> METHODS:<br/> Data sets were 5 normal rats, 4 untreated RCS rats, 7 RCS rats with dye-coupled films implanted at the age of 7 weeks after excluding unsuccessful implantation at autopsy. Behavior tests chosen were landing foot splay and visual forelimb-placing response in the menu of functional observational battery, operant-conditioning lever-press response and light/dark box test.<br/> RESULTS:<br/> Normal visual placing response was significantly less frequent in untreated RCS rats at the age of 9 and 11 weeks, compared with normal rats (P = 0.0027, chi-square test) while normal response was significantly more frequent at the age of 9 weeks in RCS rats with dye-coupled film implantation, compared with untreated RCS rats (P = 0.0221). In operant-conditioning lever-press test, the correct response rate was significantly lower in untreated RCS rats than in normal rats at the age of 9 weeks (P < 0.05, Tukey-Kramer test) while the rate was not significantly different between normal rats and RCS rats with dye-coupled film implantation. In light/dark box test, the time to enter dark box was significantly shorter in normal rats, compared with untreated RCS rats or RCS rats with dye-coupled film implantation (P < 0.05, Tukey-Kramer test).<br/> CONCLUSIONS:<br/> Behavior tests of functional observational battery, operant-conditioning lever-press response and light/dark box test discriminated vision between normal rats and RCS rats. The visual placing response and operant-conditioning lever-press test might have sensitivity to detect vision recovery in RCS rats with OUReP implantation. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 色素結合薄膜型（岡山大学方式）の人工網膜（OURePTM）の医師主導治験 223 229 EN Toshihiko Matsuo Tetsuya Uchida No potential conflict of interest relevant to this article was reported.

Springer International Publishing Acta Medica Okayama 2193-1801 3 2014 Glass transition temperature of dried lens tissue pretreated with trehalose, maltose, or cyclic tetrasaccharide 317 EN Tetsuhiro Kawata Toshihiko Matsuo Tetsuya Uchida [PURPOSE] Glass transition temperature is a main indicator for amorphous polymers and biological macromolecules as materials, and would be a key for understanding the role of trehalose in protecting proteins and cells against desiccation. In this study, we measured the glass transition temperature by differential scanning calorimetry of dried lens tissues as a model of a whole biological tissue to know the effect of pretreatment by trehalose and other sugars. [METHODS] Isolated porcine lenses were incubated with saline, 100 or 1000 mM concentration of trehalose, maltose, or cyclic tetrasaccharide dissolved in saline at room temperature for 150 minutes. The solutions were removed and all samples were dried at room temperature in a desiccator until no weight change. The dried tissues were ground into powder and placed in a measuring pan for differential scanning calorimetry. [RESULTS] The glass transition temperature of the dried lens tissues, as a mean and standard deviation, was 63.0 ± 6.4°C (n = 3) with saline pretreatment; 53.0 ± 0.8°C and 56.3 ± 2.7°C (n = 3), respectively, with 100 and 1000 mM trehalose pretreatment; 56.0 ± 1.6°C and 55.8 ± 1.1°C (n = 3), respectively, with 100 and 1000 mM maltose pretreatment; 60.0 ± 8.8°C and 59.2 ± 6.3°C (n = 3), respectively, with 100 and 1000 mM cyclic tetrasaccharide pretreatment. The glass transition temperature appeared lower, although not significantly, with trehalose and maltose pretreatments than with saline and cyclic tetrasaccharide pretreatments (P > 0.05, Kruskal-Wallis test). The glass transition temperature of the dried lens tissues with trehalose pretreatment appeared more noticeable on the thermogram, compared with other pretreatments. [CONCLUSIONS] The glass transition temperature was measured for the first time in the dried lens tissues as an example of a whole biological tissue and might provide a basis for tissue preservation in the dried condition. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1434-7229 16 3 2013 Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama-University-type retinal prosthesis 343 351 EN Alamusi Toshihiko Matsuo Osamu Hosoya Kimiko M. Tsutsui Tetsuya Uchida We have developed a photoelectric dye-coupled polyethylene film as a prototype of retinal prosthesis, which we named Okayama University-type retinal prosthesis. The purposes of this study are to conduct behavior tests to assess vision in Royal College of Surgeons (RCS) rats that underwent subretinal implantation of the dye-coupled film and to reveal retinal response to the dye-coupled film by immunohistochemistry. Polyethylene films were made of polyethylene powder at refined purity, and photoelectric dyes were coupled to the film surface at higher density compared with the prototype. Either dye-coupled film or dye-uncoupled plain film used as a control was implanted subretinally from a scleral incision in both eyes of an RCS rat at 6 weeks of the age. Behavior tests 2, 4, 6, and 8 weeks after implantation were conducted by observing head turning or body turning in the direction consistent with clockwise or counterclockwise rotation of a black-and-white-striped drum around a transparent cage housed with the rat. After the behavior tests at 8 weeks, rats' eyes were enucleated to confirm subretinal implantation of the films and processed for immunohistochemistry. In the behavior tests, the number of head turnings consistent with the direction of the drum rotation was significantly larger in RCS rats with dye-coupled- compared with plain-film implantation [P < 0.05, repeated-measure analysis of variance (ANOVA), n = 7]. The number of apoptotic neurons was significantly smaller in eyes with dye-coupled- compared with plain-film implantation (P < 0.05, Mann-Whitney U test, n = 6). In conclusion, subretinal implantation of photoelectric dye-coupled films restored vision in RCS rats and prevented the remaining retinal neurons from apoptosis. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 31 1 1996 Synthesis and Characterization of Poly[(benzo[1,2-d:5,4-d']bisthiazole-2,6-diyl)-1,4-phenylene] 11 17 EN Tetsuya Uchida Kaoru Shimamura 10.18926/19624 Poly[(benzo[1,2-d:5,4-d']bissthiazole-2,6-diyl)-1,4-phenylene](cis-PBZT)with a relatively high molecular weight was prepared by a new synthesis route. Properties of the synthesized polymer, such as thermostability, liquid crystallinity etc. were investigated and compared with those of trans-PBZT. cis-PBZT was crystallized from dilute solution and the electron microscopy showed that the precipitate was a rod-like crystal similar to that of trans form. In spite of rigid nature of the back bone, cis-PBZT showed poor crystallinity. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 31 1 1996 Solution-Grown Crystals of Poly(p-phenylene benzobisthiazole) 5 10 EN Kaoru Shimamura Tetsuya Uchida 10.18926/19622 Rigid polymer poly(p-phenylene benzobisthiazole) was crystallized from dilute solution. Electron microscopy showed that upon quenching, flat fibrils with several nm thick were produced. Subsequent heat treatment in solvent changed the fibril into "shish-kebab". On the other hand, by isothermal crystallization, an aggregate of parallel rod-like crystals was obtained. The molecular chains were accommodated normal to the rod. Based on the observation of crystal morphology, the isothermal crystallization mechanism was proposed. Because of regidity of polymer chains and wide distribution of the molecular length, the chain ends were inevitably included within the crystals resulting in crystal defects such as axial shift, lattice curvature and edge dislocation which were directly observed by lattice imaging. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 35 1-2 2001 Scanning Probe Microscopy of Poly(p-phenylene benzobisthiazole) Lamellar Crystal 35 40 EN Kaoru Shimamura Tetsuya Uchida Tomohiro Inoue 10.18926/15352 Rigid polymer, poly(p-phenylene benzobisthiazole), formed lamellar crystals where the molecular chains were oriented perpendicular to the lamellae. It was supposed that, because of wide distribution in the chain length, the lamellar surface bristled with the chain cilia among which many voids were included. Crystallographically, this region afforded us a transitional structure from full to deficient packings of chains. The structure was analyzed using the scanning probe microscope. In the course the method for imaging one molecular chain end was developed. From the images it was concluded that an isolated long cilius did not move so violently at room temperature. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 35 1-2 2001 Synthesis of Poly(ethylene-block-vinylalcohol)for Use as Amphiphilic Film Surface at High Temperature 29 34 EN Kaoru Shimamura Tetsuya Uchida 10.18926/15350 Poly (ethylene-block-vinyl alcohol), which consisted of both hydrophobic and hydrophilic blocks, was prepared by using polyethylene single crystals as starting material. Polyethylene single crystals reacted with fuming nitric acid resulting in long methylene chains with functional groups such as COOH and NO(2) at the ends (the chain length were almost same as the lamellar thickness of polyethylene single crystal). The functionalized methylene chains were allowed to react with 4-aminostyrene to give corresponding amides, i.e., methylene chains with vinyl groups at the ends (macromer). The macromers were extended by block-copolymerization with vinyl acetate, then saponified resulting in PE/PVA block co-polymer. The block copolymer was molded into sheets which were subsequently heat-treated in contact with hydrophilic or hydrophobic media. Depending on the media, the sheet surface changed at high temperature reversibly from hydrophilic to hydrophobic and vice versa. The surface property was fixed by quenching because both blocks were able to crystallize. Thus the surface of this material can be tailored for various purposes at high temperature, and then used in stable at room temperature. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 39 1 2005 Immobilization of Photoelectric Dye on the Polyethylene FilmSurface 16 20 EN Tetsuya Uchida Sanae Ishimaru Kaoru Shimamura Akihito Uji Toshihiko Matsuo Hiroshi Ohtsuki 10.18926/14136 PE film was treated with fuming nitric acid at 80℃ for 20 min, resulting in introduction of COOH moieties on the film surface. The COOH’s were reacted with ethylenediamine, whose amino groups were used for linking with (2-[4-(dibutylamino)phenyl]ethenyl)-3-carboxy-methylbenzo-thiazolium, photoelectric dye (NK-5962), which absorbs visible light and converts the photon energy to electric potentials. The dye molecules were immobilized on the PE film surface and they were able to stimulate chick retinal tissues on incidence of visible light. These facts hopefully lead to development of an artificial retinal prosthesis. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2002 剛直高分子の結晶および架橋体の構造に関する研究 EN No potential conflict of interest relevant to this article was reported.