Source 1primary paper2014Proceedings of the National Academy of Sciences
Toolkit/LiGluR-MAG0(460)
LiGluR-MAG0(460)
Also known as: light-gated ionotropic glutamate receptor, LiGluR, MAG0(460), maleimide-azobenzene-glutamate 0
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)).
Usefulness & Problems
Why this is useful
LiGluR-MAG0(460) is a light-gated mammalian ion channel system used to restore retinal light responses in blindness models. The abstract states that the second-generation photoswitch MAG0(460) enables visible-light function with peak efficiency at 460 nm.; restoring retinal light responses in blindness models; visible-light activation of engineered retinal neurons; vision restoration studies in rodent and canine photoreceptor degeneration models
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LiGluR-MAG0(460) is a light-gated mammalian ion channel system used to restore retinal light responses in blindness models. The abstract states that the second-generation photoswitch MAG0(460) enables visible-light function with peak efficiency at 460 nm.
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restoring retinal light responses in blindness models
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visible-light activation of engineered retinal neurons
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vision restoration studies in rodent and canine photoreceptor degeneration models
Problem solved
It addresses vision loss settings where photoreceptors are lost but second- and third-order retinal neurons remain. Specifically, it improves on prior UV-light LiGluR stimulation by enabling visible-light retinal restoration.; shifts LiGluR-based retinal restoration from UV stimulation to visible light
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It addresses vision loss settings where photoreceptors are lost but second- and third-order retinal neurons remain. Specifically, it improves on prior UV-light LiGluR stimulation by enabling visible-light retinal restoration.
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shifts LiGluR-based retinal restoration from UV stimulation to visible light
Problem links
shifts LiGluR-based retinal restoration from UV stimulation to visible light
LiteratureIt addresses vision loss settings where photoreceptors are lost but second- and third-order retinal neurons remain. Specifically, it improves on prior UV-light LiGluR stimulation by enabling visible-light retinal restoration.
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It addresses vision loss settings where photoreceptors are lost but second- and third-order retinal neurons remain. Specifically, it improves on prior UV-light LiGluR stimulation by enabling visible-light retinal restoration.
Published Workflows
Objective: Restore visual function in blindness models with spared inner retinal neurons by expressing LiGluR and using a visible-light photoswitch in retinal ganglion cells or ON-bipolar cells.
Why it works: The abstract frames the strategy around the fact that many inherited blindness forms spare second- and third-order retinal neurons, allowing these cells to be rendered light responsive by LiGluR plus a visible-light photoswitch.
light-gated activation of a mammalian ion channelreactivation of spared second- and third-order retinal neurons after photoreceptor losstargeted expression in retinal ganglion cells or ON-bipolar cellsphotoswitch-based optical controlretinal explant electrophysiologybehavioral testinglarge-animal tolerability assessment
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Techniques
No technique tags yet.
Target processes
translationInput: Light
Implementation Constraints
cofactor dependency: requires exogenous cofactorencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementoperating role: regulatorswitch architecture: multi component
The system requires LiGluR expression in retinal neurons and use of the MAG0(460) photoswitch. The abstract also describes retinal explant recordings, behavioral testing in mice, and intravitreal delivery in dogs.; targeted expression in retinal ganglion cells or ON-bipolar cells; photoswitch component MAG0(460) must be used with LiGluR; light stimulation near the visible-light efficiency peak is implied
The abstract does not show restoration of native photoreceptors or human clinical efficacy. It also does not establish that one retinal target cell class is universally superior across all visual functions.; requires expression targeting to retinal neurons such as RGCs or ON-bipolar cells; requires administration of both LiGluR and the photoswitch MAG0(460)
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successLarge Animalapplication demodogrod-cone dystrophy dog modelretina
Inferred from claim c5 during normalization. In a rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in retinal ganglion cells restored robust light responses in retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo. Derived from claim c5. Quoted text: In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo.
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Supporting Sources
Ranked Claims
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)
In blind rd1 mouse retinal explants, LiGluR-MAG0(460) targeted to retinal ganglion cells produced robust and uniform light-evoked firing.
In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs
LiGluR-MAG0(460) restored retinal function in visible light in rodent and canine models of blindness.
Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)).
peak efficiency wavelength 460 nm
In a rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in retinal ganglion cells restored robust light responses in retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo.
In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo.
Results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.
The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.
Approval Evidence
1 source6 linked approval claimsfirst-pass slug liglur-mag0-460
Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)).
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behavioral restorationsupports
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.
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cell targeting effectsupports
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)
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cell targeting effectsupports
In blind rd1 mouse retinal explants, LiGluR-MAG0(460) targeted to retinal ganglion cells produced robust and uniform light-evoked firing.
In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs
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functional restorationsupports
LiGluR-MAG0(460) restored retinal function in visible light in rodent and canine models of blindness.
Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)).
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large animal translationsupports
In a rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in retinal ganglion cells restored robust light responses in retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo.
In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo.
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translational positioningsupports
Results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.
The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.
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Comparisons
Source-stated alternatives
The abstract contrasts targeting LiGluR-MAG0(460) to retinal ganglion cells versus ON-bipolar cells. Upstream summary materials also identify related retinal restoration comparators, but the abstract itself does not directly benchmark against other actuator classes.
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The abstract contrasts targeting LiGluR-MAG0(460) to retinal ganglion cells versus ON-bipolar cells. Upstream summary materials also identify related retinal restoration comparators, but the abstract itself does not directly benchmark against other actuator classes.
Source-backed strengths
peak efficiency at 460 nm; restored retinal and behavioral visual functions in mouse models; restored retinal explant light responses in a canine blindness model; intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo in dogs
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peak efficiency at 460 nm
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restored retinal and behavioral visual functions in mouse models
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restored retinal explant light responses in a canine blindness model
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intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo in dogs
Compared with cLIPS1
LiGluR-MAG0(460) and cLIPS1 address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control; same primary input modality: light
Relative tradeoffs: looks easier to implement in practice; may avoid an exogenous cofactor requirement.
Compared with optogenetic systems adapted to regulate gene expression
LiGluR-MAG0(460) and optogenetic systems adapted to regulate gene expression address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control; same primary input modality: light
Relative tradeoffs: looks easier to implement in practice; may avoid an exogenous cofactor requirement.
Compared with prime-editing
LiGluR-MAG0(460) and prime-editing address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control; same primary input modality: light
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.