Transforming Growth Factor: β3 Regulates Cell Metabolism in Corneal Keratocytes and Fibroblasts

  • D. Karamichos
  • J. M. Asara
  • J. D. Zieske
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


Corneal keratocytes (HCKs) are specialized cells that reside in the corneal stroma, the largest layer of the human cornea. HCKs play a major role in corneal transparency and orchestrate corneal wound healing upon injury. Following an injury to the cornea HCKs adjacent to the wound undergo apoptosis and HCKs outside the wound area are activated, and they assume the role of remodeling the damaged stroma. Once activated the cells are termed fibroblasts (HCF). One of the key factors of this activation is thought to be transforming growth factor-beta (TGF-β). Five TGF-β (-β1,-β2,-β3,-β4, and -β5) have been identified and three (-β1,-β2, and -β3) are found in humans. We have recently identified TGF-β3 as a growth factor that can reduce or rescue corneal fibrosis in vitro. In this chapter, we present evidence that TGF-β3 plays a major role in regulating the metabolism of both HCKs and HCFs in vitro. We investigated both a conventional monolayer 2D system and a 3D self-assembled extracellular matrix (ECM) model. We targeted a total of 256 endogenous water-soluble metabolites by LC-MS/MS of which more than 60 were significantly regulated between different groups. These findings are expected to help achieve a better understanding of the specific and redundant functions of these metabolites.


Metabolomics Keratocytes Fibroblasts Corneal stroma 



Extracellular matrix




Human corneal fibroblasts


Human corneal keratocytes


Tricarboxylic acid cycle


Transforming growth factor-beta



This work was supported by National Institutes of Health Grant EY023568 (D.K) and EY020886 (DK and JDZ)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of OphthalmologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Division of Signal Transduction and Mass Spectrometry Core, Beth Israel Deaconess Medical Center and the Department of MedicineHarvard Medical SchoolBostonUSA
  3. 3.Schepens Eye Research Institute/Massachusetts Eye and Ear and the Department of OphthalmologyHarvard Medical SchoolBostonUSA

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