June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Role of Fibroblast Growth Factor Receptor 2 (FGFR2) in Corneal Stromal Thinning.
Author Affiliations & Notes
  • Roy Joseph
    School of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Akosua Konadu Boateng
    School of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Om P Srivastava
    School of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Roy Joseph None; Akosua Boateng None; Om Srivastava None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 104 – A0202. doi:
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      Roy Joseph, Akosua Konadu Boateng, Om P Srivastava; Role of Fibroblast Growth Factor Receptor 2 (FGFR2) in Corneal Stromal Thinning.. Invest. Ophthalmol. Vis. Sci. 2022;63(7):104 – A0202.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The Fibroblast Growth Factor Receptor 2 (FGFR2) is a membrane-spanning tyrosine kinase that mediates signaling of fibroblast growth factors (FGFs). It regulates embryogenesis, angiogenesis, tissue homeostasis and wound repair. It also plays an important role in cell functions such as proliferation, differentiation, apoptosis and migration. Our earlier results showed that FGFR2 was significantly down-regulated in keratocytes of human keratoconus corneal stroma. To determine the functional and mechanistic roles of FGFR2-mediated signaling in keratocytes during corneal development, a stromal specific FGFR2 knockout (KO) mouse was developed.

Methods : FGFR2 KO mouse model was generated by the following methodology: FGFR2 flox mice (Jackson Labs) were crossed with inducible keratocyte specific-Cre mice (Kera-rtTA/tet-O-Cre, Dr. Winston Kao, University of Cincinnati). The pregnant females were fed doxycycline chow (600 mg/kg) to induce corneal stromal-specific FGFR2 KO pups. The flox-, Cre-, and wild-type (wt) mice were used as controls. Corneal thickness were determined using an ultra-high resolution spectral domain optical coherence tomography instrument (SDOCT, Bioptigen). Both males and female mouse were analyzed by OCT at different ages. The topography and pachymetry maps were obtained using an OCT based method. Tunel assay and immunohistochemical analysis were performed to determine the apoptotic cells and collagen 1 expression in KO corneas relative to controls, respectively.

Results : Gene-expression analysis showed that among the two isoforms of FGFR2 (FGFR2-iiib [epithelial-specific] and FGFR2-iiic [mesenchymal specific]), FGFR2-iiic was expressed in the normal corneal stroma. OCT-based analysis of the FGFR2 KO mice (n=20) corneas showed localized stromal thinning compared to control mice (n=20). Some of the mice even developed anterior synechia (iris attached to the anterior cornea), which has been reported in human keratoconus. Immunohistochemical analysis showed relatively lower expression in collagen1 and more apoptotic cells in the FGFR2 KO corneal stroma compared to control mice stroma.

Conclusions : The FGFR2 KO mice showed localized stromal thinning similar to that seen in human keratoconus cornea. This suggested that the stromal-specific conditional FGFR2 KO mouse model would elucidate functional and mechanistic roles of FGFR2 in stromal keratocytes and also serve as a keratoconus animal model

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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