Comparison of AAV-Mediated Optogenetic Vision Restoration between Retinal Ganglion Cell Expression and ON Bipolar Cell Targeting
| Autor: | Tushar H. Ganjawala, Andrea Krstevski, Gary W. Abrams, Qi Lu, Zhuo-Hua Pan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Visual acuity genetic structures lcsh:QH426-470 Retinal bipolar cell Channelrhodopsin Biology Optogenetics Blindness Retinal ganglion Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics medicine Pupillary light reflex lcsh:QH573-671 Retinal degenerative disease Molecular Biology CAG promoter lcsh:Cytology Retinal mGluR6 promoter knockout mouse model pupillary light reflex lcsh:Genetics 030104 developmental biology medicine.anatomical_structure chemistry Retinal ganglion cell 030220 oncology & carcinogenesis Optomotor response Molecular Medicine sense organs medicine.symptom Neuroscience Retinal gene therapy |
| Zdroj: | Molecular Therapy: Methods & Clinical Development, Vol 18, Iss, Pp 15-23 (2020) Molecular Therapy. Methods & Clinical Development |
| ISSN: | 2329-0501 |
| Popis: | The loss of photoreceptors in individuals with retinal degenerative diseases leads to partial or complete blindness. Optogenetic therapy is a promising approach for restoring vision to the blind. Multiple strategies have been employed by targeting genetically encoded light sensors, particularly channelrhodopsins, to surviving retinal neurons in animal models. In particular, the strategy of targeting retinal bipolar cells has commonly been expected to result in better vision than ubiquitous expression in retinal ganglion cells. However, a direct comparison of the channelrhodopsin-restored vision between these two strategies has not been performed. Here, we compared the restored visual functions achieved by adeno-associated virus (AAV)-mediated expression of a channelrhodopsin in ON-type bipolar cells and retinal ganglion cells driven by an improved mGluR6 promoter and a CAG promoter, respectively, in a blind mouse model by performing electrophysiological recordings and behavioral assessments. Unexpectedly, the efficacy of the restored vision based on light sensitivity and visual acuity was much higher following ubiquitous retinal ganglion cell expression than that of the strategy targeting ON-type bipolar cells. Our study suggests that, at least based on currently available gene delivery techniques, the expression of genetically encoded light sensors in retinal ganglion cells is likely a practical and advantageous strategy for optogenetic vision restoration. Graphical Abstract The strategy of targeting retinal bipolar cells has been considered advantageous for optogenetic vision restoration. Here, Lu and colleagues report that AAV-mediated ubiquitous expression of a channelrhodopsin in retinal ganglion cells shows higher functional efficacy of the restored vision than ON-type bipolar cell targeting in a mouse model of blindness. |
| Databáze: | OpenAIRE |
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