June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
IGF1 and EGF act synergistically to mediate lens fiber differentiation: a process dependent on FGFR-signaling
Author Affiliations & Notes
  • Tammy So
    Anatomy & Histology, The University of Sydney, Sydney, NSW, Australia
  • Frank J Lovicu
    Anatomy & Histology, The University of Sydney, Sydney, NSW, Australia
  • Footnotes
    Commercial Relationships Tammy So, None; Frank Lovicu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4837. doi:https://doi.org/
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      Tammy So, Frank J Lovicu; IGF1 and EGF act synergistically to mediate lens fiber differentiation: a process dependent on FGFR-signaling. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4837. doi: https://doi.org/.

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

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Abstract

Purpose: Fibroblast growth factors (FGFs) are well established as primary inducers of fiber differentiation. In vitro studies have shown that a relatively high dose of FGF, comparable to vitreous humor, can induce lens fiber differentiation, as can a lower dose of FGF when combined with other ocular-derived growth factors, including platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF1) or epidermal growth factor (EGF). In the lens, these ‘co-growth factors’ act primarily as mitogens, and here we attempt to better characterise the role they play in lens fiber differentiation.

Methods: Rat lens epithelial explants were cultured with either bovine vitreous (v/v 50%), a high dose of FGF2 (100 ng/ml), IGF1 (50 ng/ml), EGF (5 ng/ml) or a combination of IGF1 and EGF (IGF1/EGF) for up to 5-days. A selective FGF receptor (FGFR) antagonist, SU5402, was used for inhibitory studies. Immunolabeling was used to localize fiber differentiation markers including β-crystallin and Prox1, as well as downstream intracellular signaling molecules including the phosphorylation of fibroblast receptor substrate 2 alpha (FR2Sα). Explants were also stained with periodic acid-Schiff to examine cell morphology.

Results: IGF1 or EGF both stimulated lens cell proliferation; however, in combination, IGF1 and EGF synergistically induced a lens fiber differentiation response, with the development of multicellular lentoid bodies expressing β-crystallin and Prox1, similar to features of vitreous- and FGF-induced lens fiber differentiation. Most interestingly, IGF1/EGF-induced lens fiber differentiation was dependent on FGFR-signaling, with downstream phosphorylation of FR2Sα. This IGF1/EGF-fiber differentiation response was also inhibited in the presence of SU5402.

Conclusions: IGF1/EGF-induced lens fiber differentiation appears to directly involve FGFR-mediated signaling. This finding supports an essential requirement for FGFR-signaling in lens fiber differentiation, and highlights a putative novel mechanism for the activation of FGFR-signaling via other independent ocular growth factors, such as IGF1 and EGF.

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