Evidence mapPaperPMID 40215317Full record

ArticleScience advances2025

Female sex hormones exacerbate retinal neurodegeneration.

Ashley A Rowe, Mauricio J Velasquez, Jacob W Aumeier, Sofia Reyes, Tiffany Yee, Emily R Nettesheim, Jeffrey G McDonald, Katherine J Wert

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Selective deletion ofiScience · 2026
    Article
  5. Review
  6. Article
  7. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Ashley A RoweDepartment of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-4202-7079
Mauricio J VelasquezCenter for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA.
Jacob W AumeierDepartment of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.
Sofia ReyesDepartment of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0009-0007-2381-2094
Tiffany YeeDepartment of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-8709-8017
Emily R NettesheimDepartment of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-8581-1205
Jeffrey G McDonaldCenter for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1570-4142
Katherine J WertDepartment of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-8430-2916

Funding

Tissue Culture & Antibody Production CoreP01HL160487 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · 2022 to 2025
$17.1M
UT Southwestern Center for Translational MedicineUL1TR003163 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$7.5M
UT Southwestern NORCP30DK127984 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$1.2M
Stem Cell, Organoid and Cell Phenotyping ModuleP30EY030413 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$656k
Mechanisms of Disease and Translational ScienceT32GM131945 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$377k
Investigating the Role of Systemic Sex Hormones on Photoreceptor DegenerationF31EY036730 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$41k
NCATS NIH HHS UL1 TR003163NEI NIH HHS F31 EY036730NEI NIH HHS P30 EY030413NEI NIH HHS R21 EY034597NHLBI NIH HHS P01 HL160487NIDDK NIH HHS P30 DK127984NIGMS NIH HHS T32 GM131945
6 · The paper itself

Abstract

Neurodegenerative disorders such as Alzheimer's disease and macular degeneration represent major sources of human suffering, yet factors influencing disease severity remain poorly understood. Sex has been implicated as one modifying factor. Here, we show that female sex is a risk factor for worsened outcomes in a model of retinal degeneration and that this susceptibility is caused by the presence of female-specific sex hormones. The adverse effect of female sex hormones was specific to diseased retinal neurons, and depletion of these hormones ameliorated this phenotypic effect, while reintroduction worsened rates of disease in females. Transcriptional analysis of retinas showed significant differences between genes involved in pyroptosis, inflammatory responses, and endoplasmic reticulum stress-induced apoptosis between males and females with retinal degeneration. These findings provide crucial insights into the pathogenesis of neurodegenerative diseases and how sex hormones can affect disease severity. These findings have far-reaching implications for clinical trial design and the use of hormonal therapy in females with certain neurodegenerative disorders.

Indexed as

Gonadal Steroid HormonesRetinal DegenerationAnimalsApoptosisDisease Models, AnimalEndoplasmic Reticulum StressFemaleHumansMaleMiceNeurodegenerative DiseasesPyroptosisRetinaSex FactorsGonadal Steroid Hormones

Identifiers

PMID40215317
PMCPMC11988432

What Socratic holds

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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 Socratic graph.