This targeting strategy places ReaChR in ON bipolar cells rather than retinal ganglion cells. In the abstract, this choice yields restored responses with richer coding properties closer to wild type.
First-pass extracted concept
ON bipolar cell targeting
Aliases
Grm6-expressing cells, ON BCs, ON BC targeting, ON-BC targeting
Extracted Explainers
What the tool is doing
Resources required
What problem it solves
It addresses the loss of visual coding richness that can occur when optogenetic therapy bypasses more of the retinal circuit. The study reports better reproducibility and broader response diversity than RGC targeting.
It provides a surviving cellular substrate for vision restoration in retinal degeneration. The study evaluates whether that substrate remains usable through later remodeling stages.
Evidence Snippets
ON bipolar (ON BCs) ... express the opsin ReaChR in Grm6- ... expressing cells
ReaChR expressed in ON-bipolar cells of the rd1 mouse
ON bipolar (ON BCs)
robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs)
Supporting Sources
Linked Claims
Compared with ON bipolar-cell targeting, retinal ganglion-cell targeting of ReaChR decreased response reproducibility and produced more stereotyped responses with reduced diversity in response polarity, contrast sensitivity, and temporal frequency tuning.
ReaChR expression targeted to ON bipolar cells and retinal ganglion cells produced equivalent response sensitivity and contrast encoding across different background irradiances in retinally degenerate mice.
Both ON bipolar-cell and retinal ganglion-cell targeting strategies restored visual responses with high fidelity, but ON bipolar-cell targeting produced a richer visual code closer to wild-type mice.
Retinal remodeling in rd1 mice does not significantly impair and may early on enhance the ability of surviving retina to support optogenetic visual restoration, implying a wide intervention window during disease progression.
Our data indicate that remodeling does not significantly impair, and at early stages may even enhance, the surviving retina's ability to support visual restoration. Clinical intervention thus remains viable throughout remodeling, suggesting a wide window in disease progression for therapeutic benefit.
Compared with ON bipolar cell targeting, retinal ganglion cell targeting decreased response reproducibility and produced more stereotyped responses with reduced diversity in response polarity, contrast sensitivity, and temporal frequency tuning.
Compared to ON BCs, targeting RGCs decreased response reproducibility and resulted in more stereotyped responses with reduced diversity in response polarity, contrast sensitivity and temporal frequency tuning.
ReaChR-evoked responses had equivalent sensitivity for ON bipolar cell targeting and retinal ganglion cell targeting and could encode contrast across different background irradiances.
For both targeting strategies, we find ReaChR-evoked responses have equivalent sensitivity and can encode contrast across different background irradiances.
Both ON bipolar cell targeting and retinal ganglion cell targeting restored visual responses with high fidelity, but ON bipolar cell targeting produced a richer visual code that more closely approached wildtype mice.
Our data show that while both approaches restore visual responses with impressive fidelity, ON BC targeting produces a richer visual code better approaching that of wildtype mice.
LiGluR-MAG0(460) targeted to either retinal ganglion cells or ON-bipolar cells in rd1 mice reinstated innate light-avoidance behavior and enabled discrimination of different temporal light patterns in an associative learning task.
LiGluR-MAG0(460) in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task.
In blind rd1 mouse retinal explants, LiGluR-MAG0(460) targeted to ON-bipolar cells produced robust but diverse activity patterns in retinal ganglion cells.
robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs)