Evidence map›Paper›PMID 38617277›Full record

ArticlebioRxiv : the preprint server for biology2024

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.

Dong Liu, Hannah C Webber, Fuyun Bian, Yangfan Xu, Manjari Prakash, Xue Feng, Ming Yang, Hang Yang, In-Jee You, Liang Li and 14 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 6 institutions in 3 countries.

Dong LiuSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Hannah C WebberSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Fuyun BianSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Yangfan XuSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Manjari PrakashInstitute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Prague West, Czechia.
Xue FengSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Ming YangSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Hang YangSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
In-Jee YouSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Liang LiSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Liping LiuSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Pingting LiuSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Haoliang HuangSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Chien-Yi ChangDepartment of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
Liang LiuSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Sahil H ShahSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Anna La TorreDepartment of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA; USA.ORCID 0000-0003-2103-4376
Derek S WelsbieViterbi Family Department of Ophthalmology, University of California San Diego, San Diego, CA; USA.
Yang SunSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Xin DuanDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA; USA.
Jeffrey Louis GoldbergSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Marcus BraunInstitute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Prague West, Czechia.ORCID 0000-0003-2026-2238
Zdenek LanskyInstitute of Biotechnology, Czech Academy of Sciences, BIOCEV, Vestec, Prague West, Czechia.
Yang HuSpencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.ORCID 0000-0002-7980-1649
Vision Eye Institute · AUCzech Academy of Sciences, Institute of Biotechnology · CZStanford University · USUniversity of California, Davis · USUniversity of California, San Francisco · USUniversity of San Diego · US

Funding

Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI TIRIN MOORE · 2017 to 2026
$8.0M
Elucidating Neuron-Intrinsic Molecular Mechanisms of Optic Nerve RegenerationR01EY024932 · NEI · TEMPLE UNIV OF THE COMMONWEALTH · PI Yang Hu · 2015 to 2026
$4.8M
Neuroprotection by Modulating ER Stress in GlaucomaR01EY023295 · NEI · TEMPLE UNIV OF THE COMMONWEALTH · PI HU, YANG · 2013 to 2022
$3.8M
The role of primary cilia in glaucoma pathogenesisR01EY025295 · NEI · STANFORD UNIVERSITY · PI Yang Sun · 2016 to 2026
$3.5M
In Vivo Function and Metabolism Evaluation of Glaucomatous RGCs by Two-Photon Scanning Laser OphthalmologyR01EY034353 · NEI · STANFORD UNIVERSITY · PI Yang Hu, Hao F Zhang · 2023 to 2026
$2.7M
Optineurin dysfunction induces neurodegeneration in normal tension glaucoma by a novel molecular mechanismR01EY032518 · NEI · STANFORD UNIVERSITY · PI Yang Hu · 2022 to 2026
$2.7M
Phosphoinositide signaling in glaucoma: rescue strategies for Lowe syndromeR01EY032159 · NEI · STANFORD UNIVERSITY · PI SUN, YANG · 2021 to 2024
$1.6M
Animal Research Equipment, Digital Cages & Metabolic, Avoidance, Fear Conditioning, Place Preference, Self-Administration, Open Field, & Microdialysis Systems for Translational NeuroscienceS10OD030452 · OD · STANFORD UNIVERSITY · PI SHAMLOO, MEHRDAD · 2021 to 2021
$743k
Lightsheet Microscope for Large-Scale Imaging of Cleared Tissue SamplesS10OD025091 · OD · STANFORD UNIVERSITY · PI DEISSEROTH, KARL A. · 2018 to 2018
$337k
Elucidation of the Molecular Mechanisms of Optineurin in Glaucomatous DegenerationF32EY029567 · NEI · STANFORD UNIVERSITY · PI WEBBER, HANNAH · 2019 to 2020
$122k
NEI NIH HHS F32 EY029567NEI NIH HHS P30 EY026877NEI NIH HHS R01 EY023295NEI NIH HHS R01 EY024932NEI NIH HHS R01 EY025295NEI NIH HHS R01 EY032159NEI NIH HHS R01 EY032518NEI NIH HHS R01 EY034353NIH HHS S10 OD025091NIH HHS S10 OD030452
6 · The paper itself

Abstract

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

Identifiers

PMID38617277
PMCPMC11014509
OpenAlexW4394065240

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.