Faculty Collaboration Database

Differential Molecular Expression of Extracellular Matrix and Inflammatory Genes at the Corneal Cone Apex Drives Focal Weakening in Keratoconus. Invest Ophthalmol Vis Sci 2016 Oct 01;57(13):5372-5382

Date

10/13/2016

Pubmed ID

27732724

DOI

10.1167/iovs.16-19677

Scopus ID

2-s2.0-84991706406 (requires institutional sign-in at Scopus site)   84 Citations

Abstract

PURPOSE: In this study, we elucidated the differential expression of a set of local molecular factors in ectatic cone area of the cornea to uncover a functional cause for focal corneal weakening characteristic of the keratoconus (KC) disease.

METHODS: All human corneal samples were collected after approval of Institutional Ethics Committee and informed consent. Keratoconus patients were classified based on clinical parameters, topographical features, and structural deformity. Epithelial cells were collected from KC patients (n = 66) undergoing corneal cross-linking procedures from cone apex and periphery. Nonectatic refractive surgery patients (n = 23) served as controls. The ratio of epithelial gene expression in cone and periphery of each eye was estimated by quantitative PCR and correlated with clinical data. Similar cone versus periphery analysis was done from the KC stroma and from KC patients with Bowman's layer (BL) breach observed by anterior segment optical coherence tomography (OCT).

RESULTS: Epithelium from the cone apex of KC patients had elevated levels of inflammatory factors TNF-α, IL-6, and matrix metalloproteinase 9 (MMP-9) but reduced Lysyl oxidase (LOX) and Collagen IVA1, which also demonstrated correlation with corneal curvature and deformity parameters. Stromal gene expression from KC patients showed trends similar to epithelium. Epithelium collected from the cone apex of BL breached KC patients showed significantly elevated MMP-9, TNF-α, and IL-6 levels but reduced IL-10, tissue inhibitor of metalloproteinases 1 (TIMP-1), and Collagen IVA1 expression.

CONCLUSIONS: This study provides the first evidence that altered corneal epithelial and stromal expression of specific genes at the corneal cone apex drives focal structural weakness in KC.

Author List

Pahuja N, Kumar NR, Shroff R, Shetty R, Nuijts RM, Ghosh A, Sinha-Roy A, Chaurasia SS, Mohan RR, Ghosh A

Author

Shyam S. Chaurasia PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Cornea
Corneal Topography
Cytokines
DNA
Extracellular Matrix Proteins
Gene Expression Regulation
Humans
Inflammation
Keratoconus
Male
Middle Aged
Prognosis
Real-Time Polymerase Chain Reaction
Tomography, Optical Coherence