Tissue and cellular biomechanics during corneal wound injury and repair

Vijay Krishna Raghunathan, Sara M Thomasy, Peter Strøm, Bernardo Yañez-Soto, Shaun P. Garland, Jasmyne Sermeno, Christopher M. Reilly, Christopher J Murphy

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Corneal wound healing is an enormously complex process that requires the simultaneous cellular integration of multiple soluble biochemical cues, as well as cellular responses to the intrinsic chemistry and biophysical attributes associated with the matrix of the wound space. Here, we document how the biomechanics of the corneal stroma are altered through the course of wound repair following keratoablative procedures in rabbits. Further we documented the influence that substrate stiffness has on stromal cell mechanics.Following corneal epithelial debridement, New Zealand white rabbits underwent phototherapeutic keratectomy (PTK) on the right eye (OD). Wound healing was monitored using advanced imaging modalities. Rabbits were euthanized and corneas were harvested at various time points following PTK. Tissues were characterized for biomechanics with atomic force microscopy and with histology to assess inflammation and fibrosis. Factor analysis was performed to determine any discernable patterns in wound healing parameters.The matrix associated with the wound space was stiffest at 7. days post PTK. The greatest number of inflammatory cells were observed 3. days after wounding. The highest number of myofibroblasts and the greatest degree of fibrosis occurred 21. days after wounding. While all clinical parameters returned to normal values 400. days after wounding, the elastic modulus remained greater than pre-surgical values. Factor analysis demonstrated dynamic remodeling of stroma occurs between days 10 and 42 during corneal stromal wound repair.Elastic modulus of the anterior corneal stroma is dramatically altered following PTK and its changes coincide initially with the development of edema and inflammation, and later with formation of stromal haze and population of the wound space with myofibroblasts. Factor analysis demonstrates strongest correlation between elastic modulus, myofibroblasts, fibrosis and stromal haze thickness, and between edema and central corneal thickness. Statement of significance: Tissue biomechanics during the course of corneal wound healing is documented for the first time through atomic force microscopy, and is correlated with advanced clinical imaging and immunohistochemistry. Parameters obtained from the study are applied in a multivariate statistical model to cluster the data for better classification and monitor the wound repair process. Elastic modulus of the anterior corneal stroma is dramatically altered following wounding and correlates initially with the development of edema and inflammation, and later with formation of stromal haze and population of the wound space with myofibroblasts. Importantly, the occurrence of myofibroblasts is preceded by changes in tissue mechanics, which is important to consider in light of crosslinking procedures applied to treat corneal diseases.

Original languageEnglish (US)
JournalActa Biomaterialia
DOIs
StateAccepted/In press - Dec 13 2016

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Biomechanics
Biomechanical Phenomena
Myofibroblasts
Repair
Factor analysis
Elastic moduli
Tissue
Elastic Modulus
Corneal Stroma
Wounds and Injuries
Wound Healing
Atomic force microscopy
Mechanics
Statistical Factor Analysis
Fibrosis
Atomic Force Microscopy
Histology
Rabbits
Inflammation
Medical imaging

Keywords

  • Atomic force microscopy
  • Cornea
  • Extracellular matrix
  • Myofibroblast
  • Tissue biomechanics
  • Wound healing

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering
  • Molecular Biology

Cite this

Tissue and cellular biomechanics during corneal wound injury and repair. / Raghunathan, Vijay Krishna; Thomasy, Sara M; Strøm, Peter; Yañez-Soto, Bernardo; Garland, Shaun P.; Sermeno, Jasmyne; Reilly, Christopher M.; Murphy, Christopher J.

In: Acta Biomaterialia, 13.12.2016.

Research output: Contribution to journalArticle

Raghunathan, Vijay Krishna ; Thomasy, Sara M ; Strøm, Peter ; Yañez-Soto, Bernardo ; Garland, Shaun P. ; Sermeno, Jasmyne ; Reilly, Christopher M. ; Murphy, Christopher J. / Tissue and cellular biomechanics during corneal wound injury and repair. In: Acta Biomaterialia. 2016.
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