Evidence map›Paper›PMID 39641270›Full record

ArticleJCI insight2024

Dysregulation of septin cytoskeletal organization in the trabecular meshwork contributes to ocular hypertension.

Rupalatha Maddala, Pallavi Gorijavolu, Levi K Lankford, Nikolai P Skiba, Pratap Challa, Rakesh K Singh, K Saidas Nair, Hélène Choquet, Ponugoti V Rao

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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  5. Article
  6. 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

9 authors.

Rupalatha MaddalaDepartment of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
Pallavi GorijavoluDepartment of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
Levi K LankfordDepartment of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
Nikolai P SkibaDepartment of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
Pratap ChallaDepartment of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
Rakesh K SinghDepartment of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, New York, USA.
K Saidas NairDepartment of Ophthalmology, UCSF, San Francisco, California, USA.
Hélène ChoquetKaiser Permanente Northern California (KPNC), Division of Research, Oakland, California, USA.
Ponugoti V RaoDepartment of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.

Funding

A Resource for Genetic Epidemiology Research in Adult Health and AgingRC2AG036607 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI RISCH, NEIL J., SCHAEFER, CATHERINE ANN · 2009 to 2010
$24.8M
VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
Trabecular Meshwork Cytoskeletal Signaling-Regulation of Aqueous Humor OutflowR01EY018590 · NEI · DUKE UNIVERSITY · PI RAO, P VASANTHA · 2008 to 2022
$5.6M
The Role of GDF-15 in Aqueous Humor Outflow and GlaucomaR01EY028823 · NEI · DUKE UNIVERSITY · PI RAO, P VASANTHA · 2018 to 2022
$2.0M
Diversity Supplement_TorresR01EY033015 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NAIR, KAYARAT SAIDAS · 2022 to 2025
$1.6M
The Role of Refractive Error in the Etiology of GlaucomaR01EY027004 · NEI · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHOQUET, HELENE · 2017 to 2020
$1.6M
The Role of Genetic and Non-Genetic Factors and Causal Mechanisms Underlying Cataract Susceptibility For Risk PredictionR01EY033010 · NEI · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHOQUET, HELENE, LACHKE, SALIL · 2022 to 2025
$1.6M
Role of Glypicans in Trabecular Meshwork Function, IOP, and GlaucomaR01EY036373 · NEI · DUKE UNIVERSITY · PI P VASANTHA RAO · 2024 to 2026
$1.4M
NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY018590NEI NIH HHS R01 EY027004NEI NIH HHS R01 EY028823NEI NIH HHS R01 EY033010NEI NIH HHS R01 EY033015NEI NIH HHS R01 EY036373NIA NIH HHS RC2 AG036607
6 · The paper itself

Abstract

Ocular hypertension, believed to result partly from increased contractile activity, cell adhesive interactions, and stiffness within the trabecular meshwork (TM), is a major risk factor for glaucoma, a leading cause of blindness. However, the identity of molecular mechanisms governing organization of actomyosin and cell adhesive interactions in the TM remains limited. Based on our previous findings, in which proteomics analyses revealed elevated levels of septins, including septin-9 in human TM cells treated with the ocular hypertensive agent dexamethasone, here, we evaluated the effects of septin-9 overexpression, deficiency, and pharmacological targeting in TM cells. These studies demonstrated a profound impact on actomyosin organization, cell adhesion, contraction, and phagocytosis. Overexpression raised intraocular pressure (IOP) in mice, while inhibition increased cell permeability. In addition, we replicated a significant association between a common variant (rs9038) in SEPT9 with IOP in the Genetic Epidemiology Research on Adult Healthy and Aging (GERA) cohort. Collectively, these data reveal a link between dysregulated septin cytoskeletal organization in the TM and increased IOP, likely due to enhanced cell contraction, adhesive interactions, and fibrotic activity. This suggests that targeting the septin cytoskeleton could offer a novel approach for lowering IOP in patients with glaucoma.

Indexed as

CytoskeletonIntraocular PressureOcular HypertensionSeptinsTrabecular MeshworkActomyosinAnimalsCell AdhesionDexamethasoneFemaleGlaucomaHumansMaleMicePhagocytosisActomyosinDexamethasoneSEPTIN9 protein, humanSeptinsCell biologyCell migration/adhesionCytoskeletonOphthalmology

Identifiers

PMID39641270
PMCPMC11623952

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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.