Transplanted neurons integrate into adult retinas and respond to light

Praseeda Venugopalan; Yan Wang; Tu Nguyen; Abigail Huang; Kenneth J. Muller; Jeffrey L. Goldberg

doi:10.1038/ncomms10472

Transplanted neurons integrate into adult retinas and respond to light

Praseeda Venugopalan, Yan Wang, Tu Nguyen, Abigail Huang, Kenneth J. Muller, Jeffrey L. Goldberg

Physiology & Biophysics

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP⁺ axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON-OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs.

Original language	English (US)
Article number	10472
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10472
State	Published - Feb 4 2016

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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title = "Transplanted neurons integrate into adult retinas and respond to light",

abstract = "Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP+ axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON-OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs.",

author = "Praseeda Venugopalan and Yan Wang and Tu Nguyen and Abigail Huang and Muller, {Kenneth J.} and Goldberg, {Jeffrey L.}",

note = "Funding Information: We thank T. Schmidt, M. Do and K.-W. Yau for their valuable input into the technique of retinal electrophysiology. We gratefully acknowledge funding from the BrightFocus Foundation and the National Eye Institute (P30-EY022589, UCSD), as well as an unrestricted grant from Research to Prevent Blindness, Inc. All confocal images were generated at the UCSD Microscopy Core (supported by NIH P30 core grant NS047101).",

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AU - Nguyen, Tu

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AU - Muller, Kenneth J.

AU - Goldberg, Jeffrey L.

N1 - Funding Information: We thank T. Schmidt, M. Do and K.-W. Yau for their valuable input into the technique of retinal electrophysiology. We gratefully acknowledge funding from the BrightFocus Foundation and the National Eye Institute (P30-EY022589, UCSD), as well as an unrestricted grant from Research to Prevent Blindness, Inc. All confocal images were generated at the UCSD Microscopy Core (supported by NIH P30 core grant NS047101).

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N2 - Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP+ axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON-OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs.

AB - Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP+ axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON-OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs.

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