Neural and angiogenic defects in eyes of transgenic mice expressing a dominant-negative FGF receptor in the pigmented cells

Fibroblast growth factors (FGF) are multipotent cytokines with demonstrated mitogenic, neurotrophic and angiogenic properties. There is evidence that they have multiple functions during and after development of the vertebrate eve. Amongst these, the role of FGF receptor mediated signaling in the ret inal pigmented epithelium (RPE) is not yet well understood. FGF-2 is produc ed in RPE cells and may play a role in photoreceptor development and/or sur vival in vivo. It may also stimulate growth of melanocytes and angiogenesis in the choroid. To address these questions, we have specifically disrupted FGF signaling by generating lines of transgenic mice expressing dominant-n egative FGF receptor 1 (FGFR-1) in the pigmented cells. Histological analys is of the eyes were conducted on hemizygous and homozygous mice at differen t ages. In homozygotes, eye growth is strongly impaired during embryogenesi s leading to massive eye degeneration seen in the early post-natal stages. In hemizygotes, the choroid is thinned and the finger-like junctions betwee n RPE cells and photoreceptors are disrupted. Scanning electron microscopy of the choroid vasculature showed that choriocapillary density, diameter an d branching are strongly affected. As mice age, they develop progressive re tinal degeneration as evidenced by photoreceptor cell loss. Our results are in agreement with the hypothesis that FGF signaling in the RPE participate s in photoreceptor survival in vivo. Our model provides evidence that FGF s ignaling is also involved in choroidal angiogenesis by a process that could relate to induction of terminal branching. (C) 2000 Academic Press.