Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy

Degenerative diseases of the retina are responsible for the death of photoreceptors and subsequent loss of vision in patients. Nevertheless, the inner retinal layers remain intact over an extended period of time, enabling the restoration of light sensitivity in blind retinas via the expression of op...

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Autores principales:	Jakub Kralik, Sonja Kleinlogel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	optogenetic gene therapy mGluR6 Opto-GPCRs vision restoration retinal degeneration ON-bipolar cells Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/cabb37ec0c264beb8e9f7eb8c7b3d0f2
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spelling	oai:doaj.org-article:cabb37ec0c264beb8e9f7eb8c7b3d0f22021-11-11T16:58:30ZFunctional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy10.3390/ijms2221115151422-00671661-6596https://doaj.org/article/cabb37ec0c264beb8e9f7eb8c7b3d0f22021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11515https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Degenerative diseases of the retina are responsible for the death of photoreceptors and subsequent loss of vision in patients. Nevertheless, the inner retinal layers remain intact over an extended period of time, enabling the restoration of light sensitivity in blind retinas via the expression of optogenetic tools in the remaining retinal cells. The chimeric Opto-mGluR6 protein represents such a tool. With exclusive ON-bipolar cell expression, it combines the light-sensitive domains of melanopsin and the intracellular domains of the metabotropic glutamate receptor 6 (mGluR6), which naturally mediates light responses in these cells. Albeit vision restoration in blind mice by Opto-mGluR6 delivery was previously shown, much is left to be explored in regard to the effects of the timing of the treatment in the degenerated retina. We performed a functional evaluation of Opto-mGluR6-treated murine blind retinas using multi-electrode arrays (MEAs) and observed long-term functional preservation in the treated retinas, as well as successful therapeutical intervention in later stages of degeneration. Moreover, the treatment decreased the inherent retinal hyperactivity of the degenerated retinas to levels undistinguishable from healthy controls. Finally, we observed for the first time micro electroretinograms (mERGs) in optogenetically treated animals, corroborating the origin of Opto-mGluR6 signalling at the level of mGluR6 of ON-bipolar cells.Jakub KralikSonja KleinlogelMDPI AGarticleoptogenetic gene therapymGluR6Opto-GPCRsvision restorationretinal degenerationON-bipolar cellsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11515, p 11515 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	optogenetic gene therapy mGluR6 Opto-GPCRs vision restoration retinal degeneration ON-bipolar cells Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	optogenetic gene therapy mGluR6 Opto-GPCRs vision restoration retinal degeneration ON-bipolar cells Biology (General) QH301-705.5 Chemistry QD1-999 Jakub Kralik Sonja Kleinlogel Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
description	Degenerative diseases of the retina are responsible for the death of photoreceptors and subsequent loss of vision in patients. Nevertheless, the inner retinal layers remain intact over an extended period of time, enabling the restoration of light sensitivity in blind retinas via the expression of optogenetic tools in the remaining retinal cells. The chimeric Opto-mGluR6 protein represents such a tool. With exclusive ON-bipolar cell expression, it combines the light-sensitive domains of melanopsin and the intracellular domains of the metabotropic glutamate receptor 6 (mGluR6), which naturally mediates light responses in these cells. Albeit vision restoration in blind mice by Opto-mGluR6 delivery was previously shown, much is left to be explored in regard to the effects of the timing of the treatment in the degenerated retina. We performed a functional evaluation of Opto-mGluR6-treated murine blind retinas using multi-electrode arrays (MEAs) and observed long-term functional preservation in the treated retinas, as well as successful therapeutical intervention in later stages of degeneration. Moreover, the treatment decreased the inherent retinal hyperactivity of the degenerated retinas to levels undistinguishable from healthy controls. Finally, we observed for the first time micro electroretinograms (mERGs) in optogenetically treated animals, corroborating the origin of Opto-mGluR6 signalling at the level of mGluR6 of ON-bipolar cells.
format	article
author	Jakub Kralik Sonja Kleinlogel
author_facet	Jakub Kralik Sonja Kleinlogel
author_sort	Jakub Kralik
title	Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
title_short	Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
title_full	Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
title_fullStr	Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
title_full_unstemmed	Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
title_sort	functional availability of on-bipolar cells in the degenerated retina: timing and longevity of an optogenetic gene therapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cabb37ec0c264beb8e9f7eb8c7b3d0f2
work_keys_str_mv	AT jakubkralik functionalavailabilityofonbipolarcellsinthedegeneratedretinatimingandlongevityofanoptogeneticgenetherapy AT sonjakleinlogel functionalavailabilityofonbipolarcellsinthedegeneratedretinatimingandlongevityofanoptogeneticgenetherapy
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Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy

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