Both acidic and basic forms of fibroblast growth factor (aFGF and bFGF) have inductive effects on lens epithelial cells in culture. There is also evidence that FGF is present in various ocular tissues, including some lens epithelial cells. The central hypothesis of this project is that FGF plays a key role in events in lens development, including morphogenesis, growth and maintenance. The project has two primary aims: (1) To determine which lens cells are (or likely to be) exposed to FGF during embryonic and postnatal development. Specific questions are: (a) What is the distribution of FGF in the eye? Immunolocalization of aFGF and bFGF in lens and associated tissues will be carried out using rats of various embryonic and postnatal stages of development; (b) Where is FGF produced in the eye? At the same developmental stages, mRNA for aFGF and bFGF will be localized by in situ hybridization; (2) To examine the functional significance of FGF (whether produced by lens cells or outside the lens) in the lens. Specific questions are: (a) Does lens-derived FGF have biological activity? Proliferative responses of explants exposed to lens-conditioned medium (with or without FGF antibodies) will be determined; (b) Is there a relationship between patterns of cell proliferation and FGF distribution in the lens? Immunohistochemistry will be used to quantify and compare spatial patterns of proliferation and FGF distribution in lenses throughout development. In some experiments cultured lenses will also be used; (c) Is cell proliferation in the lens blocked by FGF inhibitors? The effects of specific antibodies and other inhibitors on spatial patterns of proliferation in cultured lenses will be assessed as in previous section; (d) Does vitreous contain more FGF than aqueous? FGF activity will be assessed using lens explants and standard assay including immunoneutralization; aFGF and bFGF will also be quantified by ELISA; (e) Does exposure to FGF induce central epithelial cells to behave like peripheral cells? A combination of techniques already described will be used. This work is fundamental to understanding how the normal lens forms, grows and is maintained throughout life. This is important for understanding the nature of developmental abnormalities, including growth abnormalities, and may also provide the basis for understanding at least some of the subtle changes that lead to cataract.
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