Loss of Sarm1 reduces retinal ganglion cell loss in chronic glaucoma

Huilan Zeng; Jordan E Mayberry; David Wadkins; Nathan Chen; Daniel W Summers; Markus H Kuehn

doi:10.1186/s40478-024-01736-9

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Loss of Sarm1 reduces retinal ganglion cell loss in chronic glaucoma

Journal article

Open access

Peer reviewed

Loss of Sarm1 reduces retinal ganglion cell loss in chronic glaucoma

Huilan Zeng, Jordan E Mayberry, David Wadkins, Nathan Chen, Daniel W Summers and Markus H Kuehn

Acta neuropathologica communications, Vol.12(1), 23

02/08/2024

DOI: 10.1186/s40478-024-01736-9

PMCID: PMC10854189

PMID: 38331947

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Abstract

Glaucoma is one of the leading causes of irreversible blindness worldwide and vision loss in the disease results from the deterioration of retinal ganglion cells (RGC) and their axons. Metabolic dysfunction of RGC plays a significant role in the onset and progression of the disease in both human patients and rodent models, highlighting the need to better define the mechanisms regulating cellular energy metabolism in glaucoma. This study sought to determine if Sarm1, a gene involved in axonal degeneration and NAD+ metabolism, contributes to glaucomatous RGC loss in a mouse model with chronic elevated intraocular pressure (IOP). Our data demonstrate that after 16 weeks of elevated IOP, Sarm1 knockout (KO) mice retain significantly more RGC than control animals. Sarm1 KO mice also performed significantly better when compared to control mice during optomotor testing, indicating that visual function is preserved in this group. Our findings also indicate that Sarm1 KO mice display mild ocular developmental abnormalities, including reduced optic nerve axon diameter and lower visual acuity than controls. Finally, we present data to indicate that SARM1 expression in the optic nerve is most prominently associated with oligodendrocytes. Taken together, these data suggest that attenuating Sarm1 activity through gene therapy, pharmacologic inhibition, or NAD+ supplementation, may be a novel therapeutic approach for patients with glaucoma.

Glaucoma

RGC loss

Neuroprotection

NAD+ metabolism

SARM1

Axonal degeneration

Details

Title: Subtitle: Loss of Sarm1 reduces retinal ganglion cell loss in chronic glaucoma
Creators: Huilan Zeng - First Affiliated Hospital of University of South China
Jordan E Mayberry - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, 52246, USA
David Wadkins - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, 52246, USA
Nathan Chen - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, 52246, USA
Daniel W Summers - University of Iowa
Markus H Kuehn - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, 52246, USA. markus-kuehn@uiowa.edu
Resource Type: Journal article
Publication Details: Acta neuropathologica communications, Vol.12(1), 23
DOI: 10.1186/s40478-024-01736-9
PMID: 38331947
PMCID: PMC10854189
NLM abbreviation: Acta Neuropathol Commun
eISSN: 2051-5960
Grant note: I01 RX002860 / RRD VA R01 EY034534 / NEI NIH HHS
Language: English
Date published: 02/08/2024
Academic Unit: Iowa Neuroscience Institute; Orthopedics and Rehabilitation; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9984557841202771

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