Regulation of FGF soluble receptor type 1 (SR1) expression and distribution in developing, degenerating, and FGF2-treated retina.

Abstract

The spatial and temporal patterns of expression and content of the fibroblast growth factor (FGF) soluble receptor SR1, a specific inhibitor of FGF, were investigated during embryonic and postnatal development of the retina in Fisher rats. As early as at embryonic day 18 (E18), SR1 mRNA and protein were detected in the retina. SR1 protein was strongly associated with the differentiating ganglion cells and its distribution paralleled the radial pattern of retinal development, from center to periphery. From E18 to postnatal day 5, the levels of both SR1 mRNA and SR1 protein remained constant. Thereafter, they decreased rapidly, by a factor of 5 in the adult retina. SR1 was labeled in the inner nuclear layer, but never in the photoreceptor nuclei. In the neural retina of RCS dystrophic rats, the levels SR1 mRNA and SR1 protein were 2 to 3 times higher than those in the normal congenic controls, before and during photoreceptor degeneration. These results provide the first evidence that a natural FGF inhibitor is regulated during retina development and degeneration and suggest that changes in SR1 content may be involved in the regulation of FGF activities in retina. This was confirmed in vivo in RCS rats, in which delayed photoreceptor apoptosis by intravitreal injection of FGF2 was accompanied by a downregulation of SR1 expression. Dev Dyn 2000;217:24-36.