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Editors Selection IGR 9-3
Basic science: Single-RGC detection of functional impairment
Comment by Francesca Cordeiro on:
106408 Longitudinal in vivo Ca imaging reveals dynamic activity changes of diseased retinal ganglion cells at the single-cell level, Li L; Feng X; Fang F et al., Proceedings of the National Academy of Sciences of the United States of America, 2022; 119: e2206829119
Li et al. report a new electrophysiological in-vivo imaging technique for measuring the activity of retinal ganglion cells (RGCs) in two models, optic nerve crush (ONC) and silicon oil-induced hypertension (SOHU) using a genetically encoded calcium indicator called jGCaMP7s. This was expressed in RGCs four weeks after intravitreal injections of AAV2- mSncg-jGCaMP7, and visualized using confocal scanning laser ophthalmoscopy (cSLO) in response to UV light stimuli. The signal imaged showed changes in intracellular calcium concentration and thereby RGC activity, but only after complex data analysis from processed videos involving filtering, mean intensity calculations of ROI, thresholding, segmentation, and normalization.
The method allows for non-invasive and high-throughput visualization of the activity of thousands of RGCs in response to visual stimulation
The method allows for non-invasive and high-throughput visualization of the activity of thousands of RGCs in response to visual stimulation, with all the advantages offered by longitudinal study of the same eye over time. It also has the potential to identify functional/ activity biomarkers for optic neuropathies and other neurodegenerative diseases associated with RGC degeneration.
The use of UV light and the need for intravitreal AAV injection makes this difficult technology for clinical translation
However, as acknowledged by the authors, unlike the 'ex-vivo patch-clamp' method, it does not directly measure the electrical activity of individual RGCs. The results themselves are not absolute quantitative measurements. Furthermore, the use of UV light and the need for intravitreal AAV injection makes this difficult technology for clinical translation. Nonetheless, it could provide valuable information in primate models.
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