Evidence map›Paper›PMID 26247724›Full record

ArticleCell death & disease2015

DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma.

K-Y Kim, G A Perkins, M S Shim, E Bushong, N Alcasid, S Ju, M H Ellisman, R N Weinreb, W-K Ju

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
10.8field-weighted citation impact, top 1% of its field
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

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.

  1. Pooled it
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  15. Restoring AIBP expression in the retina provides neuroprotection in glaucoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  16. Protein misfolding and mitochondrial dysfunction in glaucoma.Frontiers in cell and developmental biology · 2025
    Review
  17. Article
  18. Axonal mitophagy in retinal ganglion cells.Cell communication and signaling : CCS · 2024
    Review
  19. Article
  20. Article

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

K-Y KimDepartment of Neuroscience, Center for Research in Biological Systems, National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
G A PerkinsDepartment of Neuroscience, Center for Research in Biological Systems, National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
M S ShimLaboratory for Optic Nerve Biology, Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego, La Jolla, CA, USA.
E BushongDepartment of Neuroscience, Center for Research in Biological Systems, National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
N AlcasidDepartment of Neuroscience, Center for Research in Biological Systems, National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
S JuDepartment of Neuroscience, Center for Research in Biological Systems, National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
M H EllismanDepartment of Neuroscience, Center for Research in Biological Systems, National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
R N WeinrebLaboratory for Optic Nerve Biology, Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego, La Jolla, CA, USA.
W-K JuLaboratory for Optic Nerve Biology, Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego, La Jolla, CA, USA.
University of California, San Diego · US

Funding

VOLUMETRIC CONTOUR-BASED SURFACE RECONSTRUCTIONP41RR004050 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PASQUALE, ELENA B · 1989 to 2011
$28.0M
IVEM and Image Analysis ResourceP41GM103412 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2012 to 2019
$17.9M
Vision BiostatisticsP30EY022589 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Derek Stuart Welsbie · 2012 to 2026
$10.3M
Mitochondrial Dysfunction in Glaucomatous Optic NeuropathyR01EY018658 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JU, WONKYU · 2009 to 2017
$3.5M
NCRR NIH HHS P41 RR004050NEI NIH HHS EY018658NEI NIH HHS P30 EY022589NEI NIH HHS P30EY022589NEI NIH HHS R01 EY018658NIGMS NIH HHS P41 GM103412NIGMS NIH HHS P41GM103412-24
6 · The paper itself

Abstract

Glaucoma is the leading cause of irreversible blindness and is characterized by slow and progressive degeneration of the optic nerve head axons and retinal ganglion cell (RGC), leading to loss of visual function. Although oxidative stress and/or alteration of mitochondrial (mt) dynamics induced by elevated intraocular pressure (IOP) are associated with this neurodegenerative disease, the mechanisms that regulate mt dysfunction-mediated glaucomatous neurodegeneration are poorly understood. Using a mouse model of glaucoma, DBA/2J (D2), which spontaneously develops elevated IOP, as well as an in vitro RGC culture system, we show here that oxidative stress, as evidenced by increasing superoxide dismutase 2 (SOD2) and mt transcription factor A (Tfam) protein expression, triggers mt fission and loss by increasing dynamin-related protein 1 (DRP1) in the retina of glaucomatous D2 mice as well as in cultured RGCs exposed to elevated hydrostatic pressure in vitro. DRP1 inhibition by overexpressing DRP1 K38A mutant blocks mt fission and triggers a subsequent reduction of oxidative stress, as evidenced by decreasing SOD2 and Tfam protein expression. DRP1 inhibition promotes RGC survival by increasing phosphorylation of Bad at serine 112 in the retina and preserves RGC axons by maintaining mt integrity in the glial lamina of glaucomatous D2 mice. These findings demonstrate an important vicious cycle involved in glaucomatous neurodegeneration that starts with elevated IOP producing oxidative stress; the oxidative stress then leads to mt fission and a specific form of mt dysfunction that generates further oxidative stress, thus perpetuating the cycle. Our findings suggest that DRP1 is a potential therapeutic target for ameliorating oxidative stress-mediated mt fission and dysfunction in RGC and its axons during glaucomatous neurodegeneration. Thus, DRP1 inhibition may provide a new therapeutic strategy for protecting both RGCs and their axons in glaucoma and other optic neuropathies.

Indexed as

AnimalsAxonsbcl-Associated Death ProteinDisease Models, AnimalDNA-Binding ProteinsDynaminsFemaleGene Expression RegulationGlaucomaGTP PhosphohydrolasesHigh Mobility Group ProteinsHumansIntraocular PressureMiceMice, Inbred DBAMitochondrial Dynamics3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinoneBad protein, mousebcl-Associated Death ProteinDNA-Binding ProteinsDnm1l protein, mouseDynaminsGTP PhosphohydrolasesHigh Mobility Group ProteinsP110 peptidePeptide FragmentsProtective AgentsQuinazolinonesSuperoxide DismutaseSuperoxide Dismutase 2Tfam protein, mouse

Identifiers

PMID26247724
PMCPMC4558491
OpenAlexW1080636312

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.