Cha Seongkwang, Ahn Jungryul, Kim Seong-Woo, Choi Kwang-Eon, Yoo Yongseok, Eom Heejong, Shin Donggwan, Goo Yong Sook
Department of Physiology, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea.
Horang-I Eye Center, Seoul 07999, Republic of Korea.
Bioengineering (Basel). 2023 Sep 27;10(10):1135. doi: 10.3390/bioengineering10101135.
This study aims to investigate the efficacy of electrical stimulation by comparing network-mediated RGC responses in normal and degenerate retinas using a N-methyl-N-nitrosourea (MNU)-induced non-human primate (NHPs) retinitis pigmentosa (RP) model. Adult cynomolgus monkeys were used for normal and outer retinal degeneration (RD) induced by MNU. The network-mediated RGC responses were recorded from the peripheral retina mounted on an 8 × 8 multielectrode array (MEA). The amplitude and duration of biphasic current pulses were modulated from 1 to 50 μA and 500 to 4000 μs, respectively. The threshold charge density for eliciting a network-mediated RGC response was higher in the RD monkeys than in the normal monkeys (1.47 ± 0.13 mC/cm vs. 1.06 ± 0.09 mC/cm, < 0.05) at a 500 μs pulse duration. The monkeys required a higher charge density than rodents among the RD models (monkeys; 1.47 ± 0.13 mC/cm, mouse; 1.04 ± 0.09 mC/cm, and rat; 1.16 ± 0.16 mC/cm, < 0.01). Increasing the pulse amplitude and pulse duration elicited more RGC spikes in the normal primate retinas. However, only pulse amplitude variation elicited more RGC spikes in degenerate primate retinas. Therefore, the pulse strategy for primate RD retinas should be optimized, eventually contributing to retinal prosthetics. Given that RD NHP RGCs are not sensitive to pulse duration, using shorter pulses may potentially be a more charge-effective approach for retinal prosthetics.
本研究旨在通过使用N-甲基-N-亚硝基脲(MNU)诱导的非人灵长类动物(NHPs)视网膜色素变性(RP)模型,比较正常和退化视网膜中网络介导的视网膜神经节细胞(RGC)反应,来研究电刺激的疗效。成年食蟹猴被用于正常视网膜以及MNU诱导的外层视网膜变性(RD)研究。网络介导的RGC反应是从安装在8×8多电极阵列(MEA)上的周边视网膜记录的。双相电流脉冲的幅度和持续时间分别从(1)到(50)微安和(500)到(4000)微秒进行调制。在(500)微秒的脉冲持续时间下,引发网络介导的RGC反应的阈值电荷密度在RD猴子中高于正常猴子((1.47±0.13)毫库仑/平方厘米对(1.06±0.09)毫库仑/平方厘米,(P<0.05))。在RD模型中,猴子比啮齿动物需要更高的电荷密度(猴子:(1.47±0.13)毫库仑/平方厘米,小鼠:(1.04±0.09)毫库仑/平方厘米,大鼠:(1.16±0.16)毫库仑/平方厘米,(P<0.01))。增加脉冲幅度和脉冲持续时间会在正常灵长类动物视网膜中引发更多的RGC尖峰。然而,在退化的灵长类动物视网膜中只有脉冲幅度变化会引发更多的RGC尖峰。因此,灵长类动物RD视网膜的脉冲策略应该进行优化,最终有助于视网膜假体。鉴于RD NHP的RGC对脉冲持续时间不敏感,使用更短的脉冲可能对视网膜假体来说是一种更有效的电荷利用方法。