Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina
Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of inner retinal neurons is a promising avenue to restore vision in retinas having lost their photoreceptors. Expression of optogenetic proteins in sur...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050123001407 |
| _version_ | 1827793910592700416 |
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| author | Hanen Khabou Elaine Orendorff Francesco Trapani Marco Rucli Melissa Desrosiers Pierre Yger Deniz Dalkara Olivier Marre |
| author_facet | Hanen Khabou Elaine Orendorff Francesco Trapani Marco Rucli Melissa Desrosiers Pierre Yger Deniz Dalkara Olivier Marre |
| author_sort | Hanen Khabou |
| collection | DOAJ |
| description | Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of inner retinal neurons is a promising avenue to restore vision in retinas having lost their photoreceptors. Expression of optogenetic proteins in surviving ganglion cells, the retinal output, allows them to take on the lost photoreceptive function. Nonetheless, this creates an exclusively ON retina by expression of depolarizing optogenetic proteins in all classes of ganglion cells, whereas a normal retina extracts several features from the visual scene, with different ganglion cells detecting light increase (ON) and light decrease (OFF). Refinement of this therapeutic strategy should thus aim at restoring these computations. Here we used a vector that targets gene expression to a specific interneuron of the retina called the AII amacrine cell. AII amacrine cells simultaneously activate the ON pathway and inhibit the OFF pathway. We show that the optogenetic stimulation of AII amacrine cells allows restoration of both ON and OFF responses in the retina, but also mediates other types of retinal processing such as sustained and transient responses. Targeting amacrine cells with optogenetics is thus a promising avenue to restore better retinal function and visual perception in patients suffering from retinal degeneration. |
| first_indexed | 2024-03-11T18:25:20Z |
| format | Article |
| id | doaj.art-b78a68eae9bd436db9cd81cc7fa020a7 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-03-11T18:25:20Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-b78a68eae9bd436db9cd81cc7fa020a72023-10-14T04:44:49ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012023-12-0131101107Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retinaHanen Khabou0Elaine Orendorff1Francesco Trapani2Marco Rucli3Melissa Desrosiers4Pierre Yger5Deniz Dalkara6Olivier Marre7Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France; Corresponding author: Olivier Marre, Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, 75012 Paris, France.Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of inner retinal neurons is a promising avenue to restore vision in retinas having lost their photoreceptors. Expression of optogenetic proteins in surviving ganglion cells, the retinal output, allows them to take on the lost photoreceptive function. Nonetheless, this creates an exclusively ON retina by expression of depolarizing optogenetic proteins in all classes of ganglion cells, whereas a normal retina extracts several features from the visual scene, with different ganglion cells detecting light increase (ON) and light decrease (OFF). Refinement of this therapeutic strategy should thus aim at restoring these computations. Here we used a vector that targets gene expression to a specific interneuron of the retina called the AII amacrine cell. AII amacrine cells simultaneously activate the ON pathway and inhibit the OFF pathway. We show that the optogenetic stimulation of AII amacrine cells allows restoration of both ON and OFF responses in the retina, but also mediates other types of retinal processing such as sustained and transient responses. Targeting amacrine cells with optogenetics is thus a promising avenue to restore better retinal function and visual perception in patients suffering from retinal degeneration.http://www.sciencedirect.com/science/article/pii/S2329050123001407vision restorationretinaoptogeneticsgene therapy |
| spellingShingle | Hanen Khabou Elaine Orendorff Francesco Trapani Marco Rucli Melissa Desrosiers Pierre Yger Deniz Dalkara Olivier Marre Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina Molecular Therapy: Methods & Clinical Development vision restoration retina optogenetics gene therapy |
| title | Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina |
| title_full | Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina |
| title_fullStr | Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina |
| title_full_unstemmed | Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina |
| title_short | Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina |
| title_sort | optogenetic targeting of aii amacrine cells restores retinal computations performed by the inner retina |
| topic | vision restoration retina optogenetics gene therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2329050123001407 |
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