The functional characteristics of optogenetic gene therapy for vision restoration.
Moritz LindnerMichael James GilhooleyStuart N PeirsonSteven HughesMark W HankinsPublished in: Cellular and molecular life sciences : CMLS (2020)
Optogenetic strategies to restore vision in patients blind from end-stage retinal degenerations aim to render remaining retinal neurons light-sensitive. We present an innovative combination of multi-electrode array recordings together with a complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally degenerated mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated using bipolar-cell targeted gene-delivery approaches. As clinical trials are commencing, these data provide important new information on the capacity and limitations of channelrhodopsin-based gene therapies. The toolset we established enables comparing optogenetic constructs and stem-cell-based techniques, thereby providing an efficient and sensitive starting point to identify future approaches for vision restoration.
Keyphrases
- gene therapy
- optical coherence tomography
- diabetic retinopathy
- clinical trial
- stem cells
- optic nerve
- end stage renal disease
- electronic health record
- single cell
- genome wide
- newly diagnosed
- ejection fraction
- sars cov
- spinal cord
- big data
- bipolar disorder
- machine learning
- prognostic factors
- high resolution
- cell therapy
- type diabetes
- adipose tissue
- randomized controlled trial
- skeletal muscle
- copy number
- spinal cord injury
- artificial intelligence
- metabolic syndrome
- gene expression
- health information
- drug delivery
- data analysis
- transcription factor
- patient reported outcomes
- carbon nanotubes