Evidence map›Paper›PMID 39957408›Full record

ArticleAging cell2025

Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice.

Olivia Chowdhury, Sridhar Bammidi, Pooja Gautam, Vishnu Suresh Babu, Haitao Liu, Peng Shang, Ying Xin, Emma Mahally, Mihir Nemani, Victoria Koontz and 18 more

Abstract read
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

28 authors.

Olivia ChowdhuryDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Sridhar BammidiDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pooja GautamDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Vishnu Suresh BabuDepartment of Ophthalmology, The Wilmer Eye Institute, the Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Haitao LiuDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Peng ShangDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Ying XinDepartment of Ophthalmology, The Wilmer Eye Institute, the Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Emma MahallyDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Mihir NemaniDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Victoria KoontzDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Kira LathropDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Katarzyna M KedzioraDepartment of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jonathan FranksDepartment of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Ming SunDepartment of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Joshua W SmithJohns Hopkins Mass Spectrometry and Proteomics Facility, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Lauren R DeVineJohns Hopkins Mass Spectrometry and Proteomics Facility, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Robert N ColeJohns Hopkins Mass Spectrometry and Proteomics Facility, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Nadezda StepichevaDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Anastasia StrizhakovaDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Sreya ChattopadhyayDepartment of Physiology, University of Calcutta, Kolkata, West Bengal, India.
Stacey HoseDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jacob Samuel ZiglerDepartment of Ophthalmology, The Wilmer Eye Institute, the Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
José-Alain SahelDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jiang QianDepartment of Ophthalmology, The Wilmer Eye Institute, the Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Prasun GuhaNevada Institute of Personalized Medicine, University of Nevada, Las Vegas, Nevada, USA.
James T HandaDepartment of Ophthalmology, The Wilmer Eye Institute, the Johns Hopkins School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0003-1314-1745
Sayan GhoshDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Debasish SinhaDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.ORCID 0000-0002-1739-5577

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yuanyuan Chen · 1989 to 2026
$17.8M
Targeting lysosome/RPE heterogeneity in AMD pathobiology as a novel therapyR01EY031594 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HANDA, JAMES T, SINHA, DEBASISH · 2021 to 2024
$2.4M
Function of a lens protein betaA3/A1-crystallin in astrocytesR01EY032516 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SINHA, DEBASISH · 2022 to 2022
$398k
Deciphering the role of mitochondrial/autophagy dysfunction in regulating inflammatory processes during AMD pathogenesisK99EY033421 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GHOSH, SAYAN · 2023 to 2024
$185k
NEI NIH HHS K99 EY033421NEI NIH HHS K99EY033421NEI NIH HHS P30 EY008098NEI NIH HHS P30EY08098NEI NIH HHS R01 EY031594NEI NIH HHS R01EY031594NEI NIH HHS R01 EY032516NEI NIH HHS R01EY032516Research to Prevent Blindness Unrestricted funds to Pitt Dept of OphthalmologyUniversity of Pittsburgh School of Medicine Jennifer Salvitti Davis, MD. Chair Professorship Start-up funding
6 · The paper itself

Abstract

The mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/2) are crucial for various physiological functions. Although the role of mTORC1 in retinal pigmented epithelium (RPE) homeostasis and age-related macular degeneration (AMD) pathogenesis is established, the function of mTORC2 remains unclear. We investigated both complexes in RPE health and disease. Therefore, in this study, we have attempted to demonstrate that the specific overexpression of mammalian lethal with Sec13 protein 8 (mLST8) in the mouse RPE activates both mTORC1 and mTORC2, inducing epithelial-mesenchymal transition (EMT)-like changes and subretinal/RPE deposits resembling early AMD-like pathogenesis. Aging in these mice leads to RPE degeneration, causing retinal damage, impaired debris clearance, and metabolic and mitochondrial dysfunction. Inhibition of mTOR with TORIN1 in vitro or βA3/A1-crystallin in vivo normalized mTORC1/2 activity and restored function, revealing a novel role for the mTOR complexes in regulating RPE function, impacting retinal health and disease.

Indexed as

AutophagyEpithelial-Mesenchymal TransitionMacular DegenerationRetinal Pigment EpitheliumSignal TransductionTOR Serine-Threonine KinasesAnimalsHumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceMice, Inbred C57BLMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2mTOR protein, mouseTOR Serine-Threonine Kinasesepithelial–mesenchymal transitionmetabolic/mitochondrial changesmLST8mTOR complex 1mTOR complex 2RPE

Identifiers

PMID39957408
PMCPMC12151893

What OpenQuestion holds

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Registered trials

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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.