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

Abstract:

: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 eye. Amongst these, the role of FGF receptor mediated signaling in the retinal pigmented epithelium (RPE) is not yet well understood. FGF-2 is produced in RPE cells and may play a role in photoreceptor development and/or survival 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-negative FGF receptor 1 (FGFR-1) in the pigmented cells. Histological analysis of the eyes were conducted on hemizygous and homozygous mice at different ages. In homozygotes, eye growth is strongly impaired during embryogenesis leading to massive eye degeneration seen in the early post-natal stages. In hemizygotes, the choroid is thinned and the finger-like junctions between RPE cells and photoreceptors are disrupted. Scanning electron microscopy of the choroid vasculature showed that choriocapillary density, diameter and branching are strongly affected. As mice age, they develop progressive retinal degeneration as evidenced by photoreceptor cell loss. Our results are in agreement with the hypothesis that FGF signaling in the RPE participates in photoreceptor survival in vivo. Our model provides evidence that FGF signaling is also involved in choroidal angiogenesis by a process that could relate to induction of terminal branching.

journal_name

Exp Eye Res

authors

Rousseau B,Dubayle D,Sennlaub F,Jeanny JC,Costet P,Bikfalvi A,Javerzat S

doi

10.1006/exer.2000.0892

keywords:

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

395-404

issue

4

eissn

0014-4835

issn

1096-0007

pii

S0014-4835(00)90892-3

journal_volume

71

pub_type

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