Matsuo Toshihiko, Uchida Tetsuya, Takarabe Kenichi
Department of Ophthalmology, Okayama University Medical School and Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Japan.
J Artif Organs. 2009;12(4):213-25. doi: 10.1007/s10047-009-0471-6. Epub 2009 Dec 25.
Patients with retinitis pigmentosa lose photoreceptor cells as a result of genetic abnormalities and hence become blind. Neurons such as bipolar cells and ganglion cells remain alive even in the retina of these patients, and ganglion cells send axons to the brain as the optic nerve. The basic concept of retinal prostheses is to replace dead photoreceptor cells with artificial devices to stimulate the remaining neurons with electric currents or potentials. Photodiode arrays and digital camera-type electrode arrays are the two main approaches for retinal prostheses to stimulate retinal neurons, but these arrays have the problems of poor biocompatibility, low sensitivity, and low output of electric currents, and hence have a requirement for external electric sources (batteries). To overcome these problems, we are developing photoelectric dye-based retinal prostheses that absorb light and convert photon energy to generate electric potentials. The prototype, using a photoelectric dye-coupled polyethylene film, could induce intracellular calcium elevation in photoreceptor-lacking embryonic retinal tissues and cultured retinal neurons. The subretinal implantation of the prototype in the eyes of Royal College of Surgeons (RCS) rats led to vision recovery as proved by a behavior test. The photoelectric dye that was chosen for the prototype did not exhibit any cytotoxicity. The surface potentials of the photoelectric dye-coupled film showed a rapid on-and-off response to illumination with a threshold for light intensity as measured by a Kelvin probe system. Photoelectric dye-based retinal prostheses are thin and soft, and therefore, a sheet of the film of large size, corresponding to a large visual field, could be inserted into the vitreous and then to the subretinal space through a small opening by rolling up the film. Clinical studies of photoelectric dye-based retinal prostheses in patients with retinitis pigmentosa who lose sight will be planned after the manufacturing control and the quality control had been established for the medical device.
患有色素性视网膜炎的患者由于基因异常而失去光感受器细胞，进而失明。即使在这些患者的视网膜中，双极细胞和神经节细胞等神经元仍然存活，并且神经节细胞会将轴突作为视神经发送到大脑。视网膜假体的基本概念是用人造装置替代死亡的光感受器细胞，以电流或电势刺激剩余的神经元。光电二极管阵列和数码相机型电极阵列是视网膜假体刺激视网膜神经元的两种主要方法，但这些阵列存在生物相容性差、灵敏度低和电流输出低的问题，因此需要外部电源（电池）。为了克服这些问题，我们正在开发基于光电染料的视网膜假体，其能够吸收光并将光子能量转化为电势。使用光电染料偶联聚乙烯薄膜的原型能够在缺乏光感受器的胚胎视网膜组织和培养的视网膜神经元中诱导细胞内钙升高。将该原型植入皇家外科医学院（RCS）大鼠眼中的视网膜下，行为测试证明视力得到了恢复。用于原型的光电染料未表现出任何细胞毒性。通过开尔文探针系统测量，光电染料偶联薄膜的表面电势对光照表现出快速的开启和关闭响应，具有光强度阈值。基于光电染料的视网膜假体薄且柔软，因此，一片对应于大视野的大尺寸薄膜可以通过卷起薄膜插入玻璃体，然后通过一个小开口进入视网膜下空间。在为该医疗器械建立制造控制和质量控制之后，将计划对失明的色素性视网膜炎患者进行基于光电染料的视网膜假体的临床研究。
