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Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies

Retinal ganglion cell (RGC) death occurs after optic nerve injury due to acute trauma or chronic degenerative conditions such as optic neuropathies (e.g. glaucoma). Currently, there are no effective therapies to prevent permanent vision loss resulting from RGC death, underlining the need for researc...

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Autores principales: Xiao, Xuan, Zhao, Tantai, Miyagishima, Kiyoharu J., Chen, Shan, Li, Wei, Nadal-Nicolás, Francisco M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753557/
https://www.ncbi.nlm.nih.gov/pubmed/34253851
http://dx.doi.org/10.1038/s41374-021-00637-y
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author Xiao, Xuan
Zhao, Tantai
Miyagishima, Kiyoharu J.
Chen, Shan
Li, Wei
Nadal-Nicolás, Francisco M.
author_facet Xiao, Xuan
Zhao, Tantai
Miyagishima, Kiyoharu J.
Chen, Shan
Li, Wei
Nadal-Nicolás, Francisco M.
author_sort Xiao, Xuan
collection PubMed
description Retinal ganglion cell (RGC) death occurs after optic nerve injury due to acute trauma or chronic degenerative conditions such as optic neuropathies (e.g. glaucoma). Currently, there are no effective therapies to prevent permanent vision loss resulting from RGC death, underlining the need for research on the pathogenesis of RGC disorders. Modeling human RGC/optic nerve diseases in non-human primates is ideal because of their similarity to humans, but has practical limitations including high cost and ethical considerations. In addition, many retinal degenerative disorders are age-related making the study in primate models prohibitively slow. For these reasons, mice and rats are commonly used to model RGC injuries. However, as nocturnal mammals, these rodents have retinal structures that differ from primates - possessing less than one-tenth of the RGCs found in the primate retina. Here we report the diurnal thirteen-lined ground squirrel (TLGS) as an alternative model. Compared to other rodent models, the number and distribution of RGCs in the TLGS retina are closer to primates. The TLGS retina possesses ~600,000 RGCs with the highest density along the equatorial retina matching the location of the highest cone density (visual streak). TLGS and primate retinas also share a similar interlocking pattern between RGC axons and astrocyte processes in the retina nerve fiber layer (RNFL). In addition, using TLGS we establish a new partial optic nerve injury model that precisely controls the extent of injury while sparing a portion of the retina as an ideal internal control for investigating the pathophysiology of axon degeneration and RGC death. Moreover, in vivo optical coherence tomography (OCT) imaging and ex vivo microscopic examinations of the retina in optic nerve injured TLGS confirm RGC loss precedes proximal axon degeneration, recapitulating human pathology. Thus, the TLGS retina is an excellent model, for translational research in neurodegeneration and therapeutic neuroprotection.
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spelling pubmed-87535572022-01-12 Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies Xiao, Xuan Zhao, Tantai Miyagishima, Kiyoharu J. Chen, Shan Li, Wei Nadal-Nicolás, Francisco M. Lab Invest Article Retinal ganglion cell (RGC) death occurs after optic nerve injury due to acute trauma or chronic degenerative conditions such as optic neuropathies (e.g. glaucoma). Currently, there are no effective therapies to prevent permanent vision loss resulting from RGC death, underlining the need for research on the pathogenesis of RGC disorders. Modeling human RGC/optic nerve diseases in non-human primates is ideal because of their similarity to humans, but has practical limitations including high cost and ethical considerations. In addition, many retinal degenerative disorders are age-related making the study in primate models prohibitively slow. For these reasons, mice and rats are commonly used to model RGC injuries. However, as nocturnal mammals, these rodents have retinal structures that differ from primates - possessing less than one-tenth of the RGCs found in the primate retina. Here we report the diurnal thirteen-lined ground squirrel (TLGS) as an alternative model. Compared to other rodent models, the number and distribution of RGCs in the TLGS retina are closer to primates. The TLGS retina possesses ~600,000 RGCs with the highest density along the equatorial retina matching the location of the highest cone density (visual streak). TLGS and primate retinas also share a similar interlocking pattern between RGC axons and astrocyte processes in the retina nerve fiber layer (RNFL). In addition, using TLGS we establish a new partial optic nerve injury model that precisely controls the extent of injury while sparing a portion of the retina as an ideal internal control for investigating the pathophysiology of axon degeneration and RGC death. Moreover, in vivo optical coherence tomography (OCT) imaging and ex vivo microscopic examinations of the retina in optic nerve injured TLGS confirm RGC loss precedes proximal axon degeneration, recapitulating human pathology. Thus, the TLGS retina is an excellent model, for translational research in neurodegeneration and therapeutic neuroprotection. 2021-09 2021-07-12 /pmc/articles/PMC8753557/ /pubmed/34253851 http://dx.doi.org/10.1038/s41374-021-00637-y Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Xiao, Xuan
Zhao, Tantai
Miyagishima, Kiyoharu J.
Chen, Shan
Li, Wei
Nadal-Nicolás, Francisco M.
Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies
title Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies
title_full Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies
title_fullStr Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies
title_full_unstemmed Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies
title_short Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies
title_sort establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753557/
https://www.ncbi.nlm.nih.gov/pubmed/34253851
http://dx.doi.org/10.1038/s41374-021-00637-y
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