Evidence map›Paper›PMID 39961901›Full record

ArticleHuman cell2025

Exploring the therapeutic potential of MOTS-c in age-related macular degeneration: from cellular responses to patient-derived cybrids.

Zahra Mohtashami, Kevin Schneider, Reza Azimi, Shari Atilano, Marilyn Chwa, M Cristina Kenney, Mithalesh Kumar Singh

Abstract read
PubMed Publisher
In one paragraph

Article in Human cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

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

Zahra Mohtashami *Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, 92697, USA. zmohtash@hs.uci.edu.
Kevin SchneiderDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, 92697, USA.
Reza AzimiDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, 92697, USA.
Shari AtilanoDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, 92697, USA.
Marilyn ChwaDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, 92697, USA.
M Cristina KenneyDepartment of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, 92697, USA.
Mithalesh Kumar Singh *Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, 92697, USA. mithalesh.singh@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-1812-9860

Funding

NEI R01 EY027363
6 · The paper itself

Abstract

Age-related macular degeneration (AMD), the leading cause of irreversible vision loss in the US, is on the rise among the elderly. Uncontrolled mitochondria-derived peptide production from mtDNA disruption and 16S or 12S rRNA damage could worsen AMD. Our previous work has shown that Humanin G possesses cytoprotective effects in retinal pigment epithelial (RPE) cells. However, MOTS-c, a highly efficient mitochondrial peptide, has yet to be evaluated on retinal cell survival. In this study, we show that there are differences in effects between wild-type (wt-) and differentiated ARPE19 cells (diff-ARPE19), implying that the cellular differentiation status may influence how cells respond to MOTS-c. MOTS-c has dose-dependent effects on apoptosis, inflammation, and mitochondrial biogenesis in diff-ARPE19 cells. Lower doses (500 nM) have more significant impacts than 5 µM concentrations. In diff-ARPE19 cells, a lower dose of MOTS-c can reduce the negative impact of hypoxia on cellular survival and gene expression, including apoptosis (CASP3, CASP9), mitochondrial biogenesis (TFAM, PGC-1α), and metabolic sensor (AMPK). However, it had no significant effect on ROS levels or NRF1 expression, regardless of MOTS-c dose. Exposing diff-ARPE19 cells to varied MOTS-c dosages before and after therapy in a chemically induced hypoxic environment yields no extra benefits as compared to MOTS-c treatment alone. MOTS-c had different effects on the expression of genes linked with apoptosis, mitochondrial biogenesis, and antioxidant activity in AMD patients versus age-matched control cybrids. The MOTS-c peptide appears to enhance cellular metabolism and regulate gene expression, which could potentially provide therapeutic benefits in AMD.

Indexed as

Macular DegenerationRetinal Pigment EpitheliumApoptosisCell DifferentiationCell LineCells, CulturedCell SurvivalDose-Response Relationship, DrugGene ExpressionHumansMitochondriaOrganelle BiogenesisAge-related macular degenerationApoptosisCybridsDifferentiated ARPE19HypoxiaMitochondrial biogenesisMOTS-c

Identifiers

PMID39961901

What Socratic holds

Textmetadata
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.