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Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma

Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated...

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Autores principales: Smith, Jennie C., Zhang, Kevin Yang, Sladek, Asia, Thompson, Jennifer, Bierlein, Elizabeth R., Bhandari, Ashish, Van Hook, Matthew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794376/
https://www.ncbi.nlm.nih.gov/pubmed/36526366
http://dx.doi.org/10.1523/ENEURO.0421-22.2022
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author Smith, Jennie C.
Zhang, Kevin Yang
Sladek, Asia
Thompson, Jennifer
Bierlein, Elizabeth R.
Bhandari, Ashish
Van Hook, Matthew J.
author_facet Smith, Jennie C.
Zhang, Kevin Yang
Sladek, Asia
Thompson, Jennifer
Bierlein, Elizabeth R.
Bhandari, Ashish
Van Hook, Matthew J.
author_sort Smith, Jennie C.
collection PubMed
description Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown yet are likely to contribute to vision loss. Here, we used anatomic and physiological approaches to study the structure and function of retinogeniculate (RG) synapses in male and female DBA/2J (D2) mice with inherited glaucoma before and after IOP elevation. D2 mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals while patch-clamp measurements of RG synaptic function showed that synaptic transmission was reduced in 9-month and 12-month D2 mice because of the loss of individual RGC axon inputs. TC neuron dendrites had reduced Sholl complexity at 12 months, suggestive of delayed reorganization following reduced synaptic input. There was no detectable change in RGC density in 11- to 12-month D2 retinas, quantified as the number of ganglion cell layer-residing somata immuno-positive for NeuN and immuno-negative for the amacrine marker choline acetyltransferase (ChAT). Thus, observed synaptic defects appear to precede RGC somatic loss. These findings identify glaucoma-associated and IOP-associated deficits in an important subcortical RGC projection target, shedding light on processes linking IOP to vision loss.
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spelling pubmed-97943762022-12-28 Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma Smith, Jennie C. Zhang, Kevin Yang Sladek, Asia Thompson, Jennifer Bierlein, Elizabeth R. Bhandari, Ashish Van Hook, Matthew J. eNeuro Research Article: New Research Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown yet are likely to contribute to vision loss. Here, we used anatomic and physiological approaches to study the structure and function of retinogeniculate (RG) synapses in male and female DBA/2J (D2) mice with inherited glaucoma before and after IOP elevation. D2 mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals while patch-clamp measurements of RG synaptic function showed that synaptic transmission was reduced in 9-month and 12-month D2 mice because of the loss of individual RGC axon inputs. TC neuron dendrites had reduced Sholl complexity at 12 months, suggestive of delayed reorganization following reduced synaptic input. There was no detectable change in RGC density in 11- to 12-month D2 retinas, quantified as the number of ganglion cell layer-residing somata immuno-positive for NeuN and immuno-negative for the amacrine marker choline acetyltransferase (ChAT). Thus, observed synaptic defects appear to precede RGC somatic loss. These findings identify glaucoma-associated and IOP-associated deficits in an important subcortical RGC projection target, shedding light on processes linking IOP to vision loss. Society for Neuroscience 2022-12-21 /pmc/articles/PMC9794376/ /pubmed/36526366 http://dx.doi.org/10.1523/ENEURO.0421-22.2022 Text en Copyright © 2022 Smith et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: New Research
Smith, Jennie C.
Zhang, Kevin Yang
Sladek, Asia
Thompson, Jennifer
Bierlein, Elizabeth R.
Bhandari, Ashish
Van Hook, Matthew J.
Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma
title Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma
title_full Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma
title_fullStr Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma
title_full_unstemmed Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma
title_short Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma
title_sort loss of retinogeniculate synaptic function in the dba/2j mouse model of glaucoma
topic Research Article: New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794376/
https://www.ncbi.nlm.nih.gov/pubmed/36526366
http://dx.doi.org/10.1523/ENEURO.0421-22.2022
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