Evidence map›Paper›PMID 18469195›Full record

ArticleInvestigative ophthalmology & visual science2008

Cultured porcine trabecular meshwork cells display altered lysosomal function when subjected to chronic oxidative stress.

Paloma B Liton, Yizhi Lin, Coralia Luna, Guorong Li, Pedro Gonzalez, David L Epstein

Open access · greenAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 19% of its field
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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
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  13. Cannabidiol and the Canonical WNT/β-Catenin Pathway in Glaucoma.International journal of molecular sciences · 2021
    Review
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  15. Article
  16. Neuroinflammation in Primary Open-Angle Glaucoma.Journal of clinical medicine · 2020
    Review
  17. Autophagy in the Aging and Experimental Ocular Hypertensive Mouse Model.Investigative ophthalmology & visual science · 2020
    Article
  18. Article
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  20. Article
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

6 authors at 1 institution in 1 country.

Paloma B LitonDepartment of Ophthalmology, Duke University Eye Center, Durham, North Carolina, USA.
Yizhi Lin
Coralia Luna
Guorong Li
Pedro Gonzalez
David L Epstein
Duke University · US

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI W Daniel Stamer · 1985 to 2026
$19.3M
METABOLISM OF THE TRABECULAR MESHWORKR01EY001894 · NEI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI EPSTEIN, DAVID L · 1985 to 2011
$4.2M
Cellular Senescence and GlaucomaR01EY016228 · NEI · DUKE UNIVERSITY · PI GONZALEZ, PEDRO · 2005 to 2011
$2.2M
Oxidative Stress and Lysosomal Function in the Outflow PathwayR21EY019137 · NEI · DUKE UNIVERSITY · PI LITON, PALOMA · 2008 to 2009
$545k
NEI NIH HHS EY016228NEI NIH HHS EY01894NEI NIH HHS EY05722NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY001894NEI NIH HHS R01 EY016228NEI NIH HHS R21 EY019137
6 · The paper itself

Abstract

purposeTo investigate the effects of chronic oxidative stress on lysosomal function in trabecular meshwork (TM) cells.

methodsConfluent cultures of porcine TM cells were grown for 2 weeks in physiological (5% O(2)) or hyperoxic conditions (40% O(2)) in the presence or absence of the protease inhibitor leupeptin (10 microM). The following parameters were quantified using the fluorogenic probes indicated within parentheses: autofluorescence, intracellular reactive oxygen species (ROS; H(2)DCFDA), mitochondrial membrane potential (JC-1), mitochondrial content (Mitotracker Red; Invitrogen-Molecular Probes, Eugene, OR), lysosomal content (acridine orange and Lysotracker Red [Invitrogen-Molecular Probes]), autophagic vacuole content (MDC), SA-beta-galactosidase (FDG), and cathepsin activities (z-FR-AMC). Cathepsin levels were quantified by qPCR and Western blot analysis. Ultrastructural analysis was performed by transmission electron microscopy.

resultsProlonged exposure of porcine TM cells to a hyperoxic environment led to an increase in ROS production and oxidized material. Electron micrographs revealed the cytoplasmic accumulation of lipofuscin-loaded lysosomes. Augmented lysosomal and autophagic vacuole content was confirmed with specific fluorophores. The mRNA and protein levels of several cathepsins were upregulated with oxidative stress. This upregulated expression did not correlate with increased lysosomal activity.

conclusionsThe results indicate that chronic exposure of TM cells to oxidative stress causes the accumulation of nondegradable material within the lysosomal compartment, leading to diminished lysosomal activity. Since the lysosomal system is responsible for the continuous turnover of cellular organelles, impaired lysosomal activity may lead to progressive failure of cellular TM function with age.

Indexed as

Oxidative StressAgingAnimalsAutophagyCathepsinsCells, CulturedCell SizeHyperoxiaLysosomesMembrane PotentialsMitochondrial MembranesOxygenPolymerase Chain ReactionSwineTrabecular MeshworkVacuolesCathepsinsOxygen

Identifiers

PMID18469195
PMCPMC3601374
OpenAlexW1971066287

What OpenQuestion 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 OpenQuestion graph.