Evidence map›Paper›PMID 41357987›Full record

ArticlebioRxiv : the preprint server for biology2025

AKAP1 regulates mitochondrial and synaptic homeostasis to enable neuroprotection and repair in retinal ganglion cell degeneration.

Tonking Bastola, Keun-Young Kim, Ziyao Shen, Guy A Perkins, Muna Poudel, Veronica Gomez, Yoonjin Lim, Hyejeong Choi, Jae Yon Won, Soo-Ho Choi and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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.

No citing paper in PubMed yet.

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

13 authors.

Tonking BastolaViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.
Keun-Young KimNational Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA 92039, USA.
Ziyao ShenViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.
Guy A PerkinsNational Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA 92039, USA.
Muna PoudelViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.
Veronica GomezInstitute of Engineering in Medicine, Shu Chien - Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA 92039, USA.
Yoonjin LimViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.
Hyejeong ChoiViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.
Jae Yon WonViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.
Soo-Ho ChoiDepartment of Medicine, University of California San Diego, La Jolla, CA 92039, USA.
Mark H EllismanNational Center for Microscopy and Imaging Research, Department of Neurosciences, University of California San Diego, La Jolla, CA 92039, USA.
Robert N WeinrebViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.
Won-Kyu JuViterbi Family Department of Ophthalmology, Viterbi Family Vision Research Center, Shiley Eye Institute, University of California San Diego, La Jolla, CA 92039, USA.ORCID 0000-0003-1117-4834

Funding

Vision BiostatisticsP30EY022589 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Radha Ayyagari · 2012 to 2026
$10.3M
Mitochondrial Protection in Glaucomatous Optic NeuropathyR01EY031697 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JU, WONKYU, PERKINS, GUY A · 2020 to 2023
$2.7M
AIBP-mediated neuroprotection in glaucomatous optic neuropathyR01EY034116 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SOO-HO CHOI, WONKYU JU · 2023 to 2026
$2.6M
NEI NIH HHS P30 EY022589NEI NIH HHS R01 EY031697NEI NIH HHS R01 EY034116
6 · The paper itself

Abstract

Glaucoma is a leading cause of irreversible blindness, characterized by progressive retinal ganglion cell (RGC) loss and optic nerve degeneration. Mitochondrial dysfunction plays a central role in this neurodegeneration, yet effective targeted therapies remain limited. Here, we identify the mitochondrial scaffold A-kinase anchoring protein 1 (AKAP1) as a critical regulator of RGC resilience and axon regeneration. AKAP1 expression is diminished in human glaucomatous retinas and experimental glaucoma models, correlating with elevated intraocular pressure, disrupted mitochondrial dynamics, oxidative stress, and synaptic instability. Restoration of AKAP1 via adeno-associated virus serotype 2-mediated gene therapy preserves RGC survival, promotes mitochondrial fusion and cristae integrity, enhances ATP production, and mitigates oxidative and apoptotic stress in mouse models of glaucoma and optic nerve injury. Transcriptomic profiling of AKAP1 knockout retinas reveals widespread dysregulation of mitochondrial and synaptic gene networks. Mechanistically, AKAP1 stabilizes synapses by promoting mitochondrial biogenesis, modulating calcium/calmodulin-dependent kinase II and synapsin phosphorylation, maintaining synaptophysin expression, and suppressing complement component C1q expression, thereby preventing early synaptic loss in glaucomatous neurodegeneration. Moreover, restoring AKAP1 expression facilitates axonal regeneration, preserves the central visual pathway, and maintains visual function. Collectively, these findings establish AKAP1 as a master regulator of mitochondrial and synaptic homeostasis and axonal regeneration and a promising therapeutic target for vision preservation in glaucomatous neurodegeneration.

Identifiers

PMID41357987
PMCPMC12676536

What OpenQuestion 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 OpenQuestion graph.