Cited by 853Corneal surgery and disordersCorneal Surgery and TreatmentsCollagen: Extraction and Characterization

The DOI matches its Crossref record; 167 of the 167 references it cites were found in a registry or an index; 55 of the 152 sources its claims cite were checked for support.

Corneal structure and transparency

Open access
Meek, Keith M., Knupp, Carlo·2015·Progress in Retinal and Eye Research

Abstract

The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes current knowledge of corneal stromal architecture and transparency, emphasizing that transparency arises from collagen fibril uniformity and short-range order rather than lamellar arrangement alone. It integrates X-ray scattering, electron tomography, nonlinear microscopy, and theoretical modelling to explain how proteoglycans and type V collagen regulate fibril spacing and diameter.

Key findings

  • The stroma comprises nearly 90% of corneal thickness; the central human cornea has approximately 200 lamellae, with anterior lamellae highly interwoven and posterior lamellae less interlaced. Anterior lamellar insertions into Bowman’s layer average about 19°.
  • Transparency depends on narrow collagen fibrils with uniform diameters and restricted centre-to-centre spacing. Fibrils contain about 300–400 triple-helical molecules per cross-section and about 70 microfibrils, with axial periodicity reduced from 67 nm to closer to 65 nm.
  • Maurice calculated that independent scattering would leave only about 6% of incoming light to reach the retina; destructive interference from ordered fibrils cancels scattering in all directions except forward. If 20% of fibrils have twice the normal diameter, backward radiation arises and transparency is impaired.
  • Type V collagen limits fibril diameter, while proteoglycans maintain interfibrillar spacing. Across over 40 animal species, the volume fraction occupied by hydrated fibrils and interfibrillar GAGs was constant. Human corneal transmittance exceeds 90% between 500 and 1300 nm, reaches 80% at 380 nm, and drops at 1430 and 1950 nm due to water absorption; transmittance decreases outside the central 4 mm.

Methods

  • Narrative review of corneal stromal structure and transparency, synthesizing evidence from X-ray scattering, electron tomography, second harmonic generation and other nonlinear microscopy, spectrophotometry, and theoretical modelling.
  • Evidence base includes human, bovine, rabbit, chicken embryo, mutant mouse, and comparative data from over 40 animal species, plus unpublished results from the authors’ group.
  • Main analysis is qualitative synthesis of structural and optical studies and theoretical models; no systematic review or meta-analysis is described.

Limitations

  • Stated in the paper: X-ray scattering cannot directly image lamellae and must infer arrangement from diffraction patterns; it provides bulk averages and cannot resolve adjacent lamellae. Multiple scattering is not fully modelled, and photonic band structure theory has been applied only to a perfect hexagonal lattice. The existence of Dua’s layer/pre-Descemet’s layer remains controversial, and some cited findings are unpublished.
  • Evident from the text: as a narrative review, it does not report a systematic search strategy or quantitative synthesis, and it relies substantially on animal models and unpublished or preliminary data rather than new primary experimental data.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.preteyeres.2015.07.001

Cites

167 of 167 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

55 of 152 cited sources checked · 32 supported · 1 flagged · accuracy not yet measured

Show all 95 claims

  • Probably not a substantial claim. 26
  • It may state two separate claims as one. 65
  • The quote only partly states this claim. 2
80 of 80
  • The authors state this as an assumption.

    The secondary electromagnetic radiation scattered by any collagen fibril does not interact with other fibrils of the cornea but travels undisturbed to the retina.

    “The explanation for cornea transparency presented above is based on the approximation that the secondary electromagnetic radiation scattered by any collagen fibril will not interact with other fibrils of the cornea, but will travel undisturbed to the retina.”
  • The paper relies on this without support.

    If the cornea swells much above its physiological hydration, it begins to scatter significant quantities of light and lose transparency.

    “If the cornea swells much above its physiological hydration it begins to scatter significant quantities of light and to lose its transparency.”
  • The paper relies on this without support.

    Keratocytes themselves are transparent except for their nuclei.

    “Keratocytes themselves are transparent except for their nuclei.”
  • The paper relies on this without support.

    Structural data from real corneas can now be collected using modern techniques such as three-dimensional block face scanning electron microscopy.

    “Structural data from real corneas can now be collected using modern techniques such as three-dimensional block face scanning electron microscopy”
  • The paper relies on this without support.

    Modern computers are fast enough for transparency predictions to be obtained by solving Maxwell's equations for the collected data.

    “modern computers are fast enough for transparency predictions to be obtained by solving Maxwell's equations for the collected data”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 166 references

Research works printed but not linked: 12

  1. Dohlman, 1971, The function of the corneal epithelium in health and disease, Invest. Ophthalmol., 10, 383
  2. Feynman, 1963, vol. 1
  3. Harding, 1980, Corneal collagen: a review, Colloq. Int. Cent. Rech. Sci. Natl., 287, 51
  4. Kolmer, 1936, Handb. Der mikr, Anat. Des. Menschen (v. Möllend.), III, 2
  5. Maurice, 2001, Graft transparency is in the eye of the beholder, Invest. Ophthalmol. Vis. Sci., S282
  6. Meyer, 1948, Mucopolysaccharides and mucoids of ocular tissues, vol. 2, 71
  7. Ranvier, 1898, Influence histogénétique d’une forme antérieure, à propos de la regeneration de la membrane de Descemet, C. R. Acad. Sci. (Paris), 126, 23
  8. Rispoli, 1978, Apparecchiatura a fibre ottiche per la misura oggettiva della variazione di trasparenza corneale, Boll. Ocul., 55, 63
  9. Virchow, 1905, vol. 1, 1
  10. Von Fleischl, 1880, vol. 3, 47
  11. Weiner, 1912, Allgemeine Sätze űber die Dielektrizitätskonstanten der Mischkörper, Abh. Sachs. Ges. Akad. Wiss. Math. Phys. Kl., 6, 574
  12. White, 2014, 3D structural studies of the cornea, Ophthalmic Physiol. Opt., 34, 693

Cited by

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Items 101–200 of 853

Metadata

Authors
Meek, K. M., & Knupp, C.
Affiliations
Cardiff University (GB)
Corresponding author
Meek, Keith M.
Venue
Progress in Retinal and Eye Research
Publisher
Elsevier BV
Published
2015-11
Volume
49
Pages
1-16
ISSN
1350-9462 (ISSN-L)
OpenAlex
W1954007937
Cited by
853
References
166
Citations by year
2026: 104 · 2025: 109 · 2024: 101 · 2023: 94 · 2022: 99 · 2021: 88 · 2020: 87 · 2019: 75 · 2018: 45 · 2017: 32 · 2016: 17 · 2015: 1
FWCI
5.05
Type
journal article
Language
en
Open access
Locations
  • Progress in Retinal and Eye Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
Funders
  • MRC Programme (503626)
  • Diamond Light Source
  • ESRF
Topics
  • Health Sciences › Medicine › Ophthalmology › Corneal surgery and disorders
  • Health Sciences › Medicine › Ophthalmology › Corneal Surgery and Treatments
  • Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
Keywords
corneal stroma, corneal transparency, collagen fibrils, collagen lamellae, proteoglycans, corneal ultrastructure, optical transmittance, corneal refractive index
MeSH terms
Collagen, Cornea, Corneal Stroma, Crystallins, Humans, Microscopy, Electron, Proteoglycans, Extracellular Matrix Proteins

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