Evidence map›Paper›PMID 40205682›Full record

ArticleAutophagy2025

MLST8 overexpression in RPE cells disrupts autophagy through novel mechanisms affecting AMD pathogenesis.

Sridhar Bammidi, Sayan Ghosh, Olivia Chowdhury, Vishnu Suresh Babu, Puja Dutta, Stacey Hose, Debasish Sinha

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Spontaneous whole retinal degeneration in aged Beclin1 heterozygous mice.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Article
  4. Article
  5. Review
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

7 authors.

Sridhar BammidiDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sayan GhoshDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Olivia ChowdhuryDepartment of Physiology, University of Calcutta, Kolkata, India.
Vishnu Suresh BabuDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Puja DuttaDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Stacey HoseDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Debasish SinhaDepartment of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Funding

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
NEI NIH HHS R01 EY031594
6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, with dysfunction of the retinal pigment epithelium (RPE) central to disease pathogenesis. Using our uniquely developed MLST8 (MTOR associated protein, LST8 homolog) knock-in animal model with RPE-specific overexpression, which drives MTOR (mechanistic target of rapamycin kinase) upregulation, we demonstrate that increased MTOR complexes 1 and 2 in the RPE disrupts macroautophagy/autophagy by suppressing autophagosome formation genes and impairing MAP1LC3/LC3 processing. This leads to autophagosome accumulation and defective autolysosome formation, driving RPE dysfunction and AMD-like pathology, including subretinal debris build up and photoreceptor degeneration. Notably, MTOR inhibition with torin1 treatment or CRYBA1 overexpression rescues these defects, restoring autophagy and RPE integrity. Our findings reveal that autophagy disruption mediated by both MTORC1 and MTORC2 drives AMD-like pathology in our mouse model, establishing autophagy regulation as a promising avenue for therapeutic intervention in this vision-threatening disease.

Indexed as

Adaptor Proteins, Signal TransducingAutophagyMacular DegenerationRetinal Pigment EpitheliumAnimalsAutophagosomesDisease Models, AnimalHumansLysosomesMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceMice, Inbred C57BLTOR Serine-Threonine KinasesAdaptor Proteins, Signal TransducingMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2TOR Serine-Threonine KinasesAge-related macular degenerationautophagyMLST8MTORC1MTORC2retinal pigment epithelium

Identifiers

PMID40205682
PMCPMC12282985

What OpenQuestion holds

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Read underepoch 390

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.