Differential distribution of fibroblast growth factor receptors(FGFRs) on foveal cones: FGFR-4 is an early marker of conephotoreceptors

[摘要] Purpose: Relatively little is known of the expression anddistribution of FGF receptors (FGFR) in the primate retina. Weinvestigated expression of FGFRs in developing and adult Macaca monkeyretina, paying particular attention to the cone rich, macular region.Methods: One fetal human retina was used for diagnostic PCR usingprimers designed for FGFR1, FGFR2, FGFR3, FGFR4, and FGFR like-protein 1(FGFrl1) and for probe design to FGFR3, FGFR4, and FGFrl1. Rat cDNA wasused to synthesize probes for FGFR1 and FGFR2 with 90% and 93% homologyto human, respectively. Paraffin sections of retina from macaque fetusessacrificed at fetal days (Fd) 64, 73, 85, 105, 115, 120, and 165, andpostnatal ages 2.5 and 11 years were used to detect FGF receptors byimmunohistochemistry and in situ hybridization.Results: PCR showed each of the FGF receptors are expressed in fetalhuman retina. In situ hybridization indicated that mRNA for eachreceptor is expressed in all retinal cell layers during development, butmost intensely in the ganglion cell layer (GCL). FGFR2 mRNA is reducedin the adult inner (INL) and outer (ONL) nuclear layers, while FGFrl1mRNA is virtually absent from the adult ONL. FGFR4 mRNA is particularlyintense in fetal and adult cone photoreceptors. Immunoreactivity toFGFR1-FGFR4 was detected in the interphotoreceptor matrix in whatappeared to be RPE microvilli associated with developing photoreceptorouter segments, and generally is high in the GCL and low in the INL.Different patterns of FGFR3 and FGFR4 immunoreactivities in the outerplexiform layer (OPL) suggest localization of FGFR3 to horizontal cellprocesses, with FGFR4 being expressed by both horizontal and bipolarcell processes. FGFR1, FGFR3, and FGFR4 immunoreactivities are presentin the inner segments and somata of adult cones. The pedicles ofdeveloping and adult cones are FGFR1 and FGFR3 immunoreactive, and thebasal, synaptic region is FGFR4 immunoreactive. FGFR4 labels conesalmost in their entirety from early in development and is not detectedin rods. The fibers of Henle are intensely FGFR4 immunoreactive in adultcones.Conclusions: The results show high levels of FGF receptor expressionin developing and adult retina. Differential distribution of FGFreceptors across developing and adult photoreceptors suggests specificroles for FGF signalling in development and maintenance ofphotoreceptors, particularly the specialized cones of the fovea.

[学科分类] 生物化学/生物物理