Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy.
Samantha R De SilvaAlun R BarnardSteven HughesShu K E TamChris MartinMandeep S SinghAlona O Barnea-CramerMichelle E McClementsMatthew J DuringStuart N PeirsonMark W HankinsRobert E MacLarenPublished in: Proceedings of the National Academy of Sciences of the United States of America (2017)
Optogenetic strategies to restore vision in patients who are blind from end-stage retinal degenerations aim to render remaining retinal cells light sensitive once photoreceptors are lost. Here, we assessed long-term functional outcomes following subretinal delivery of the human melanopsin gene (OPN4) in the rd1 mouse model of retinal degeneration using an adeno-associated viral vector. Ectopic expression of OPN4 using a ubiquitous promoter resulted in cellular depolarization and ganglion cell action potential firing. Restoration of the pupil light reflex, behavioral light avoidance, and the ability to perform a task requiring basic image recognition were restored up to 13 mo following injection. These data suggest that melanopsin gene therapy via a subretinal route may be a viable and stable therapeutic option for the treatment of end-stage retinal degeneration in humans.
Keyphrases
- gene therapy
- optical coherence tomography
- diabetic retinopathy
- optic nerve
- endothelial cells
- mouse model
- end stage renal disease
- induced apoptosis
- ejection fraction
- chronic kidney disease
- poor prognosis
- sars cov
- gene expression
- dna methylation
- single cell
- neuropathic pain
- stem cells
- genome wide
- patient reported outcomes
- oxidative stress
- climate change
- spinal cord
- cell death
- mesenchymal stem cells
- endoplasmic reticulum stress