Aqueous humour- and growth factor-induced lens cell proliferation is dependent on MAPK/ERK1/2 and Akt/PI3-K signalling

Exp Eye Res. 2006 Sep;83(3):667-78. doi: 10.1016/j.exer.2006.03.008. Epub 2006 May 8.


The aqueous humour of the eye is a rich source of growth factors, many of which have been shown to be lens cell mitogens; however, the identity of the endogenous mitogen(s) for lens cells is still unknown. As a first approach to identify the mechanisms by which these aqueous humour-derived growth factors induce lens cell proliferation, the present study set out to examine MAPK/ERK1/2 and PI3-K/Akt signalling associated with lens cell proliferation. Using a lens explant system, we examined the effects of different lens mitogens (aqueous humour, FGF, PDGF, IGF and EGF) using 5'-2'-bromo-deoxyuridine incorporation. In addition, we adopted immunolabelling techniques to compare the roles that the ERK1/2 and PI3-K signalling pathways play in regulating lens cell proliferation. We showed that the aqueous humour, and all the other growth factors examined, could activate ERK1/2 and PI3-K/Akt signalling. By targeting these pathways using specific pharmacological inhibitors, we were able to show that both ERK1/2 and PI3-K signalling are required for growth factor-induced lens cell proliferation, and that there was a strong correlation between the spatial distribution of proliferating cells in lens explants with ERK1/2 labelling. Furthermore, our blocking studies confirmed that PI3-K/Akt signalling can act upstream of ERK1/2, potentiating ERK1/2 phosphorylation in growth factor-induced lens cell proliferation. A better understanding of the signalling pathways required for aqueous humour-induced lens cell proliferation may ultimately allow us to identify the mitogen(s) that are important for regulating lens cell proliferation in situ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aqueous Humor / metabolism*
  • Cattle
  • Cell Proliferation
  • Cells, Cultured
  • Epidermal Growth Factor / pharmacology
  • Epithelial Cells
  • Fibroblast Growth Factor 2 / pharmacology
  • Growth Substances / pharmacology*
  • Insulin-Like Growth Factor I / pharmacology
  • Lens, Crystalline / cytology*
  • Lens, Crystalline / enzymology
  • MAP Kinase Signaling System*
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Stimulation, Chemical


  • Growth Substances
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt