ECM stiffness modulates the proliferation but not the motility of primary corneal keratocytes in response to PDGF-BB

Krithika S. Iyer, Daniel P. Maruri, Kara E. Peak, David W. Schmidtke, W. Matthew Petroll, Victor D. Varner

Research output: Contribution to journalArticlepeer-review

Abstract

During corneal wound healing, keratocytes present within the corneal stroma become activated into a repair phenotype upon the release of growth factors, such as transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). The process of injury and repair can lead to changes in the mechanical properties of the tissue, and previous work has shown that the TGF-β1-mediated myofibroblast differentiation of corneal keratocytes depends on substratum stiffness. It is still unclear, however, if changes in stiffness can modulate keratocyte behavior in response to other growth factors, such as PDGF-BB. Here, we used a polyacrylamide (PA) gel system to determine whether changes in stiffness influence the proliferation and motility of primary corneal keratocytes treated with PDGF-BB. In the presence of PDGF-BB, cells on stiffer substrata exhibited a more elongated morphology and had higher rates of proliferation than cells in a more compliant microenvironment. Using a freeze-injury to assay cell motility, however, we did not observe any stiffness-dependent differences in the migration of keratocytes treated with PDGF-BB. Taken together, these data highlight the importance of biophysical cues during corneal wound healing and suggest that keratocytes respond differently to changes in ECM stiffness in the presence of different growth factors.

Original languageEnglish (US)
Article number109112
JournalExperimental Eye Research
Volume220
DOIs
StatePublished - Jul 2022

Keywords

  • Biomechanics
  • Corneal wound healing
  • Freeze injury
  • Mechanobiology
  • Platelet-derived growth factor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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