Osteopontin drives retinal ganglion cell resiliency in glaucomatous optic neuropathy.
CP: Neuroscience
Osteopontin
glaucoma
human retina
neuronal types
neuroprotection
optic nerve crush
retinal ganglion cell
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 09 2023
26 09 2023
Historique:
received:
21
02
2023
revised:
28
06
2023
accepted:
11
08
2023
medline:
26
10
2023
pubmed:
25
8
2023
entrez:
25
8
2023
Statut:
ppublish
Résumé
Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, αRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found an ectopic neuronal expression of Osteopontin (Spp1) in other RGCs subject to glaucomatous conditions. This contrasted with the Spp1 downregulation subject to axotomy. αRGC-specific Spp1 elimination led to significant αRGC loss, diminishing their resiliency. Spp1 overexpression led to robust neuroprotection of susceptible RGC subclasses under glaucomatous conditions. In contrast, Spp1 overexpression did not significantly protect RGCs subject to axotomy. Additionally, SPP1 marked adult human RGC subsets with large somata and SPP1 expression in the aqueous humor correlated with glaucoma severity. Our study reveals Spp1's role in mediating neuronal resiliency in glaucoma.
Identifiants
pubmed: 37624696
pii: S2211-1247(23)01049-5
doi: 10.1016/j.celrep.2023.113038
pmc: PMC10591811
mid: NIHMS1933884
pii:
doi:
Substances chimiques
Osteopontin
106441-73-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113038Subventions
Organisme : NEI NIH HHS
ID : P30 EY026877
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026942
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097305
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY029342
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY030138
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024932
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY002162
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY032518
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY023295
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.S.W. is a founder of and consultant to Perceive Biotherapeutics.
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