Evidence map›Paper›PMID 37540176›Full record

ArticleInvestigative ophthalmology & visual science2023

Effects of Cathepsin S Inhibition in the Age-Related Dry Eye Phenotype.

Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Zhiyuan Yu, Cintia S de Paiva

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 4 countries.

Jeremias G GallettiDepartment of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.
Kaitlin K ScholandDepartment of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.
Claudia M Trujillo-VargasDepartment of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.
Wolfgang HaapRoche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Tiago Santos-FerreiraRoche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Christoph UllmerRoche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Zhiyuan YuDepartment of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.
Cintia S de PaivaDepartment of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.
Baylor College of Medicine · USRoche (Switzerland) · CHRice University · USUniversidad de Antioquia · CO

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9M
VISION RESEARCH CENTERP30EY002520 · NEI · BAYLOR COLLEGE OF MEDICINE · PI Samuel M Wu · 1985 to 2026
$14.8M
P30-CENTER CORE GRANT FOR VISION RESEARCHP30EY021725 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Michelle C Callegan, MICHAEL H ELLIOTT · 2011 to 2026
$10.5M
VISUAL SCIENCEST32EY007001 · NEI · BAYLOR COLLEGE OF MEDICINE · PI Samuel M Wu · 1985 to 2026
$3.7M
Defining the interplay of interferon-gamma and cathepsin S in age-related dry eyeR01EY030447 · NEI · BAYLOR COLLEGE OF MEDICINE · PI DE PAIVA, CINTIA S. · 2020 to 2023
$1.6M
NCI NIH HHS P30 CA125123NEI NIH HHS P30 EY002520NEI NIH HHS P30 EY021725NEI NIH HHS R01 EY030447NEI NIH HHS T32 EY007001Wellcome TrustWellcome Trust 221859/Z/20/Z
6 · The paper itself

Abstract

Purpose: Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease. Methods: Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet-Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify infiltrating immune cells. The inflammatory foci (>50 cells) were counted under a 10× microscope lens and quantified using the focus score. Goblet cell density was investigated in periodic acid-Schiff stained sections. Ctss-/- mice were compared to age-matched wild-type mice. Results: Aged mice subjected to cathepsin S inhibition or Ctss-/- mice showed improved conjunctival goblet cell density and cornea mechanosensitivity. There was no change in total LG focus score in the diet or Ctss-/- mice, but there was a lower frequency of CD4+IFN-γ+ cell infiltration in the LGs. Furthermore, aged Ctss-/- LGs had an increase in T central memory, higher numbers of CD19+B220-, and fewer CD19+B220+ cells than wild-type LGs. Conclusions: Our results indicate that therapies aimed at decreasing cathepsin S can ameliorate age-related dry eye disease with a highly beneficial impact on the ocular surface. Further studies are needed to investigate the role of cathepsin S during aging.

Indexed as

Dry Eye SyndromesLacrimal ApparatusAnimalsCathepsinsDisease Models, AnimalFemaleMiceMice, Inbred C57BLMice, KnockoutPhenotypeTearscathepsin SCathepsins

Identifiers

PMID37540176
PMCPMC10414132
OpenAlexW4385564073

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.