Fibroblast growth factor receptor 4 (FGFR4) is expressed in adult rat and human retinal photoreceptors and neurons

Abstract

The fibroblast growth factor (FGF) family, with its prototype members acidic FGF (FGF-1) and basic FGF (FGF-2), binds to four related receptor tyrosine kinases, termed FGFR1, R2, R3, and R4, expressed on most types of cells in tissue culture. In many respects, the FGFR appear similar to other growth factor receptors; thus, dimerization of receptor monomers on ligand binding is likely to be a requisite for activation of the kinase domains, leading to receptor trans-phosphorylation. Within the central nervous system (CNS), including retina, FGFR1 and R2 have been widely described as the predominant forms. FGFR4 is reported to be strongly expressed only during early stages of development, and apart from one small region (the lateral habenular nucleus) is not detectable in adult CNS. Screening of different neural and nonneural tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that whereas FGFR1 and R2 were strongly expressed in adult cortex, cerebellum, retina, and kidney, robust FGFR4 expression was only seen in retina and kidney. FGFR4 mRNA was present within fractions of the outer and inner nuclear layers isolated from adult rat retinas, and could also be detected in pure photoreceptor cultures prepared from young rat retinas. On the contrary, FGFR4 mRNA could not be detected in primary cultures of retinal Müller glia or pigment epithelium, indicating specific enrichment in retinal neurons. In situ hybridization studies of adult rat retina showed FGFR4 expression in all retinal cellular layers, especially prominent in the outer nuclear layer. FGFR4 protein was detected by immunoblotting of homogenates of rat retina, with specific antibody binding to bands at 115, 47, and 30 kDa. FGFR4 mRNA and protein were also reliably detected in postmortem adult human retina. The potential roles of these signal transduction molecules in FGF-induced biological responses in the retina are discussed.