Department of Biomedical Engineering, University of Massachusetts, Amherst, MA 01003, USA.
Institute for Applied Life Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Biosensors (Basel). 2022 Dec 28;13(1):42. doi: 10.3390/bios13010042.
Electroretinography (ERG) is a non-invasive electrophysiological recording technique that detects the electrical signaling of neuronal cells in the visual system. In conventional ERG recordings, the signals are considered a collective electrical response from various neuronal cell populations, including rods, cones, bipolar cells, and retinal ganglion cells (RGCs). However, due to the limited ability to control electrophysiological responses from different types of cells, the detailed information underlying ERG signals has not been analyzed and interpreted. Linking the features of ERG signals to the specific neuronal response will advance the understanding of neuronal electrophysiological dynamics and provide more evidence to elucidate pathological mechanisms, such as RGC loss during the progression of glaucoma. Herein, we developed an advanced ERG recording system integrated with a programmable, non-invasive optogenetic stimulation method in mice. In this system, we applied an automatic and unbiased ERG data analysis approach to differentiate a, b wave, negative response, and oscillatory potentials. To differentiate the electrophysiological response of RGCs in ERG recordings, we sensitized mouse RGCs with red-light opsin, ChRmine, through adeno-associated virus (AAV) intravitreal injection. Features of RGC dynamics under red-light stimulation were identified in the ERG readout. This non-invasive ERG recording system, associated with the programmable optogenetics stimulation method, provides a new methodology to dissect neural dynamics under variable physiological and pathological conditions in vivo. With the merits of non-invasiveness, improved sensitivity, and specificity, we envision this system can be further applied for early-stage detection of RGC degeneration and functional progression in neural degenerative diseases, such as glaucoma.
视网膜电图（ERG）是一种非侵入性的电生理记录技术，用于检测视觉系统中神经元细胞的电信号。在传统的 ERG 记录中，信号被认为是来自各种神经元细胞群体的集体电响应，包括视杆细胞、视锥细胞、双极细胞和视网膜神经节细胞（RGC）。然而，由于对不同类型细胞的电生理反应的控制能力有限，ERG 信号的详细信息尚未得到分析和解释。将 ERG 信号的特征与特定的神经元反应联系起来，将有助于深入了解神经元电生理动力学，并提供更多证据来阐明病理机制，例如青光眼进展过程中 RGC 的损失。在这里，我们开发了一种先进的 ERG 记录系统，该系统与小鼠的可编程非侵入性光遗传学刺激方法相结合。在该系统中，我们应用了一种自动和无偏的 ERG 数据分析方法来区分 a、b 波、负反应和振荡电位。为了在 ERG 记录中区分 RGC 的电生理反应，我们通过腺相关病毒（AAV）玻璃体内注射使小鼠 RGC 敏化红色光视蛋白 ChRmine。在 ERG 读数中鉴定了红光刺激下 RGC 动力学的特征。这种与可编程光遗传学刺激方法相关的非侵入性 ERG 记录系统提供了一种新的方法来在体内分离可变生理和病理条件下的神经动力学。由于具有非侵入性、提高的灵敏度和特异性，我们设想该系统可以进一步应用于神经退行性疾病（如青光眼）中 RGC 变性和功能进展的早期检测。
