Evidence map›Paper›PMID 33502460›Full record

ArticleInvestigative ophthalmology & visual science2021

Regional Differences and Physiologic Behaviors in Peripapillary Scleral Fibroblasts.

Julia Szeto, Amanda Chow, Liam McCrea, Ann Mozzer, Thao D Nguyen, Harry A Quigley, Ian Pitha

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. Trial
  2. Article
  3. Decreased scleral Wnt5aNature communications · 2025
    Article
  4. Article
  5. Observational
  6. Article
  7. Review
  8. Review
  9. Article
  10. Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  11. Article
  12. Ocular Biomechanics and Glaucoma.Vision (Basel, Switzerland) · 2023
    Review
  13. Article
  14. Article
  15. 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 at 2 institutions in 1 country.

Julia SzetoDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Amanda ChowDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Liam McCreaDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Ann MozzerDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Thao D NguyenDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Harry A QuigleyDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Ian PithaDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
PATHOGENESIS OF GLAUCOMATOUS OPTIC NERVE DAMAGER01EY002120 · NEI · JOHNS HOPKINS UNIVERSITY · PI QUIGLEY, HARRY ALAN · 1985 to 2025
$12.6M
Pathogenesis of Glaucomatous Optic Nerve DamageR56EY002120 · NEI · JOHNS HOPKINS UNIVERSITY · PI QUIGLEY, HARRY ALAN · 2008 to 2008
$369k
NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY002120NEI NIH HHS R56 EY002120
6 · The paper itself

Abstract

Purpose: The purpose of this study was to describe the cellular architecture of normal human peripapillary sclera (PPS) and evaluate surface topography's role in fibroblast behavior. Methods: PPS cryosections from nonglaucomatous eyes were labelled for nuclei, fibrillar actin (FA), and alpha smooth muscle actin (αSMA) and imaged. Collagen fibrils were imaged using second harmonic generation. Nuclear density and aspect ratio of the internal PPS (iPPS), outer PPS (oPPS), and peripheral sclera were determined. FA and αSMA fibril alignment with collagen extracellular matrix (ECM) was determined. PPS fibroblasts were cultured on smooth or patterned membranes under mechanical strain and in the presence of TGFβ1 and 2. Results: The iPPS (7.1 ± 2.0 × 10-4, P < 0.0001) and oPPS (5.3 ± 1.4 × 10-4, P = 0.0013) had greater nuclei density (nuclei/µm2) than peripheral sclera (2.5 ± 0.8 × 10-4). The iPPS (2.0 ± 0.3, P = 0.002) but not oPPS (2.4 ± 0.4, P = 0.45) nuclei had smaller aspect ratios than peripheral (2.7 ± 0.5) nuclei. FA was present throughout the scleral stroma and was more aligned with oPPS collagen (9.6 ± 1.9 degrees) than in the peripheral sclera (15.9 ± 3.9 degrees, P =0.002). The αSMA fibers in the peripheral sclera were less aligned with collagen fibrils (26.4 ± 4.8 degrees) than were FA (15.9 ± 3.9 degrees, P = 0.0002). PPS fibroblasts cultured on smooth membranes shifted to an orientation perpendicular to the direction of cyclic uniaxial strain (1 Hz, 5% strain, 42.2 ± 7.1 degrees versus 62.0 ± 8.5 degrees, P < 0.0001), whereas aligned fibroblasts on patterned membranes were resistant to strain-induced reorientation (5.9 ± 1.4 degrees versus 10 ± 3.3 degrees, P = 0.21). Resistance to re-orientation was reduced by TGFβ treatment (10 ± 3.3 degrees without TGFβ1 compared to 23.1 ± 4.5 degrees with TGFβ1, P < 0.0001). Conclusions: Regions of the posterior sclera differ in cellular density and nuclear morphology. Topography alters the cellular response to mechanical strain.

Indexed as

ActinsAgedAged, 80 and overAnatomy, RegionalBiomarkersCell CountCells, CulturedCollagenFemaleFibroblastsHumansMaleMiddle AgedOptic DiskScleraTissue DonorsACTA2 protein, humanActinsBiomarkersCollagen

Identifiers

PMID33502460
PMCPMC7846956
OpenAlexW3124782371

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.